Aurein is a cationic antimicrobial peptide, rich in phenylalanine residues. Although the peptide has been extensively studied, its mechanism of action is not fully understood and has not been established. This project...Aurein is a cationic antimicrobial peptide, rich in phenylalanine residues. Although the peptide has been extensively studied, its mechanism of action is not fully understood and has not been established. This project is focused on studying the interactions of aurein with model biological membranes and antimalarials using Fourier Transform Infrared (FTIR), fluorescence, dynamic light scattering (DLS), atomic force microscopy (AFM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) techniques. FTIR data revealed conformational changes to the secondary structure of the peptide in the presence of the model membranes. The strongest interactions of aurein were found with DOPC and lipid raft systems. Fluorescence data revealed some differences in the mechanism of interaction between aurein and lipid rafts. Topographical analysis was performed using atomic force microscopy (AFM). AFM images of the peptide with its lipid rafts showed a change in surface roughness suggesting a different mechanism of interaction. DLS data in agreement with FTIR confirmed that aurein interacts differently with the lipid rafts. The results gathered from this study provided new insights on the interaction of aurein. On the other hand, drug-drug interaction issues continue to present a major dilemma for the clinician caring for complex patients such as those infected with infectious disease. This study has examined the interaction of aurein with quinine, primaquine, and chloroquine. Significant interactions between aurein and antimalarials occured at a higher concentration of antimalarials. Interactions between aurein and anti-malarials reveal a strong interaction between aurein and primaquine. Interactions between aurein and quinine or chloroquine were found to be weak and negligible. FTIR, TGA, and DSC may be used in a complementary way to gain insights into the possible drug-drug interactions involving aurein. These studies are needed to initiate in vivo controlled interaction studies between antibiotics and antimalarials.展开更多
The triterpene quassinoid ailanthinone is a structurally intricate natural product possessing highly potent antimalarial activity against multidrug resistance plasmodium parasites. Although the mechanism of action of ...The triterpene quassinoid ailanthinone is a structurally intricate natural product possessing highly potent antimalarial activity against multidrug resistance plasmodium parasites. Although the mechanism of action of ailanthinone is not completely understood, it is presumed to disrupt regular ribosomal functions by inhibiting parasite protein synthesis. Natural scarcity and low solubility of many quassinoids have impeded their development as potential clinical candidates, but exquisite potency of ailanthinone against Plasmodium remains compelling in the global fight against malaria. Herein, we report the highly selective synthesis of 1-hydroxyl derivatives of ailanthinone, including ester, carbonate, carbamate and sulfonate derivatives. The key feature of the synthesis is a one-step regioselective modification of the 1-hydroxyl group in favor of two other hydroxyl groups at C12 and C13. Derivatives were obtained via direct reaction with acyl/sulfonyl chlorides in the presence of a tertiary amine base without any protection-deprotection. In vitro antimalarial evaluations of these derivatives were compared with chloroquine and mefloquine against the Plasmodium falciparum clones, D6, W2, and TM91C235. The results demonstrate that modification of the 1-hydroxyl group is achievable, and the antimalarial activity of these derivatives relative to the parent product is significantly retained, thus paving the way for synthesis of derivatives with improved biological availability and/or increased potency.展开更多
Mice are considered to be a similar model to humans in the pathogenesis of malaria. This study evaluates the effect of parenteral antimalarials on the spleen and liver of Swiss albino mice after chronic exposure to Pl...Mice are considered to be a similar model to humans in the pathogenesis of malaria. This study evaluates the effect of parenteral antimalarials on the spleen and liver of Swiss albino mice after chronic exposure to Plasmodium berghei. After chronic exposure to P. berghei NK65 strain, the level of parasitemia was assessed.The mice were treated for 3 days using chloroquine(5 mg/kg), quinine(10 mg/kg),and artemether(2 mg/kg). The effect of chronic exposure and the pattern of recovery were evaluated. There was significant decrease in total body weight after chronic exposure to P. berghei(P < 0.05). An increase in total weight recovery was seen after day 15 of treatment with the antimalarials; this was more pronounced with artemether. A significant increase in liver and spleen weights due to P. berghei infection was seen. There was a recovery pattern due to decrease in liver and spleen weights following antimalarial administration, which was greatest with artemether(P < 0.05). Significant changes were more in parasitized, quinine and artemether groups(P < 0.05). There was a significant decrease in total spleen protein due to chloroquine but a decrease due to quinine and artemether(P < 0.05). No significant changes in liver and spleen albumin were observed after treatment. The highest parasite clearance was observed with artemether, followed by quinine. Five mice died after chronic exposure in all the groups prior to treatment. There was significant enlargement and discoloration of spleen and liver after chronic exposure. This study showed that artemether aided recovery of the liver and spleen better than quinine and chloroquine in albino mice after chronic exposure to P. berghei. This suggests there is potential for improvement in antimalarial therapy.展开更多
Malaria is a parasitic disease caused by the bite of female Anopheles mosquito and particularly affects the tropical areas of the world. According to national statistics it is the leading cause of consultations and ho...Malaria is a parasitic disease caused by the bite of female Anopheles mosquito and particularly affects the tropical areas of the world. According to national statistics it is the leading cause of consultations and hospitalizations. Nowadays, despite the surveillance systems for efficient malaria control and access to generic drugs, Benin is witnessing an increased development of illicit drug markets with a large part of the population going towards such markets. However, this is not without adverse impact on the health of individuals, as well as, the economic status of the country. Therefore, the situation needs to be seriously considered by policy makers at various levels, health professionals but also the entire international community in order to thwart this scourge.Regarding the aforementioned situation, the current study was undertaken aiming to perform a quality control of selected antimalarial drugs of the illegal market in Porto-Novo city. Therefore, 40 antimalarial batches were randomly collected in the illicit drug market and submitted to analytical tests such as: macroscopic examination (a visual and critical examination);mass uniformity test;disintegration test;identification test and active ingredients’ content measurement. At the end of the study, the percentages of non-compliance is 97.5%, 5%, 15% and 27.5%, respectively for the content uniformity tests, disintegration, identification and assay. Over-all, 42.5% of noncompliance was recorded. The findings of this study prove that street vended drugs offer no guarantee of good quality and pose a threat to the health of populations. Also, the rate of non-compliance denotes a flaw in the security of the drug distribution system.展开更多
Dear Editor,We present the reported case of rapid onset bull’s eye maculopathy.Chloroquine(CQ)and its safer,more widely used analogue,hydroxychloroquine(HCQ),were originally developed as antimalarial medications.Howe...Dear Editor,We present the reported case of rapid onset bull’s eye maculopathy.Chloroquine(CQ)and its safer,more widely used analogue,hydroxychloroquine(HCQ),were originally developed as antimalarial medications.However,they have since become essential in the treatment of various autoimmune disorders due to their anti-inflammatory and immunomodulatory properties.HCQ is also being investigated for potential applications in diabetes mellitus,coronavirus disease 2019,heart disease,and as an adjunct in cancer therapy^([1-2]).展开更多
Malaria still threatens global health seriously today.While the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors,multi-targeting inhibitors are highly desired to over...Malaria still threatens global health seriously today.While the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors,multi-targeting inhibitors are highly desired to overcome the increasingly serious drug resistance.Here,we performed a structure-based drug design on mitochondrial respiratory chain of Plasmodium falciparum and identified an extremely potent molecule,RYL-581,which binds to multiple protein binding sites of P.falciparum simultaneously(allosteric site of type Ⅱ NADH dehydrogenase,Q_(o) and Q_(i) sites of cytochrome bc_(1)).Antimalarials with such multiple targeting mechanism of action have never been reported before.RYL-581 kills various drug-resistant strains in vitro and shows good solubility as well as in vivo activity.This structurebased strategy for designing RYL-581 from starting compound may be helpful for other medicinal chemistry projects in the future,especially for drug discovery on membrane-associated targets.展开更多
Objective:To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain(Pf3D7),its clinical isolate(Pf140/SS),and Plasmodium berghei ANKA(PbA).Methods:Using ring-stage survival assay,phen...Objective:To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain(Pf3D7),its clinical isolate(Pf140/SS),and Plasmodium berghei ANKA(PbA).Methods:Using ring-stage survival assay,phenotypic assessments,and SYBR-green-based fluorescence assay,the antimalarial activities of noscapine were assessed compared with dihydroartemisinin(DHA)in in vivo and in vitro studies.In addition,hemolysis and cytotoxicity tests were carried out to evaluate its safety.RT-PCR assay was also conducted to determine the effect of noscapine on papain-like cysteine protease Plasmodium falciparum falcipain-2(PfFP-2).Results:The antimalarial efficacy of noscapine against Pf3D7 and Pf140/SS was comparable to DHA,with IC50 values of(7.68±0.88)and(5.57±0.74)nM/mL,respectively,and>95%inhibition of PbA infected rats.Noscapine also showed a safe profile,as evidenced by low hemolysis and cytotoxicity even at high concentrations.Moreover,PfFP-2 expression was significantly inhibited in both noscapine-treated Pf3D7 and Pf140/SS(P<0.01).Conclusions:Noscapine has antimalarial properties comparable to standard antimalarial DHA with better safety profiles,which may be further explored as a therapeutic candidate for the treatment of malaria.展开更多
This review provides a comprehensive overview of the phytochemistry, medicinal properties, and biological activities of the Artemisia species. Artemisia species exhibit a wide range of morphological and phytochemical ...This review provides a comprehensive overview of the phytochemistry, medicinal properties, and biological activities of the Artemisia species. Artemisia species exhibit a wide range of morphological and phytochemical diversity, showing promise for the treatment of various diseases in humans, plants, and animals. Phytochemicals found in Artemisia spp. include terpenoids, flavonoids, coumarins, caffeoylquinic acids, sterols, and acetylenes. Dietary flavonoids have been linked to reduced cell aging, lipid peroxidation, and cancer risks. Sterols, including plant sterols, play a significant role in reducing the plasma cholesterol levels. Essential oils from Artemisia plants contain volatile chemicals with antibacterial, antiviral, and antifungal properties that contribute to their biological activity. This study aimed to elucidate the effective compounds of Artemisia plants and their medicinal benefits and biological activities.展开更多
Objective:To establish the appropriateness of malaria case management at health facility level in four districts in Zambia.Methods:This study was a retrospective evaluation of the quality of malaria case management at...Objective:To establish the appropriateness of malaria case management at health facility level in four districts in Zambia.Methods:This study was a retrospective evaluation of the quality of malaria case management at health facilities in four districts conveniently sampled to represent both urban and rural settings in different epidemiological zones and health facility coverage.The review period was from January to December 2008.The sample included twelve lower level health facilities from four districts.The Pearson Chi-square test was used to identify characteristics which affected the quality of case management.Results:Out of 4891 suspected malaria cases recorded at the 12 health facilities,more than 80%of the patients had a temperature taken to establish their fever status.About 67%(CI_(95)66.1-68.7)were tested for parasitemia by either rapid diagnostic test or microscopy,whereas the remaining22.5%(CI_(95)213.1-23.7)were not subjected to any malaria test.Of the 2247 malaria cases reported(complicated and uncomplicated),71%were parasitologicaily confirmed while 29%were clinically diagnosed(unconfirmed).About 56%.(CI_(95)53.9-58.1)of the malaria cases reported were treated with artemether-lumefantrine(AL),35%(CI_(95)33.1-37.0)with sulphadoxine-pyrimethamine,8%(CI_(95)6.9-9.2)with quinine and 1%did not receive any anti-malarial.Approximately 30%of patients WHO were found negative for malaria parasites were still prescribed an anti-malarial,contrary to the guidelines.There were marked inter-district variations in the proportion of patients in WHOm a diagnostic tool was used,and in the choice of anti-malarials for the treatment of malaria confirmed cases.Association between health worker characteristics and quality of case malaria management showed that nurses performed better than environmental health technicians and clinical officers on the decision whether to use the rapid diagnostic test or not.Gender,in service training on malaria,years of residence in the district and length of service of the health worker at the facility were not associated with diagnostic and treatment choices.Conclusions:Malaria case management was characterised by poor adherence to treatment guidelines.The non-adherence was mainly in leans of:inconsistent use of confirmatory tests(rapid diagnostic test or microscopy)for malaria;prescribing anti-malarials which are not recommended(e.g.sulphadoxine-pyrimethamine)and prescribing anti-malarials to cases testing negative.Innovative approaches are required to improve health worker adherence to diagnosis and treatment guidelines.展开更多
Objective:To evaluate the antiplasmodial activity of Phyllanthus(P.)amarus crude ethanol leaf extract and its effects on semen quality in male BALB/c mice.Methods:A total of 36 adult mice were divided into six groups,...Objective:To evaluate the antiplasmodial activity of Phyllanthus(P.)amarus crude ethanol leaf extract and its effects on semen quality in male BALB/c mice.Methods:A total of 36 adult mice were divided into six groups,with 6 mice each.Five groups were infected with Plasmodium(P.)berghei,and one group was left uninfeceted.Of the five infected groups,one group was left untreated,three groups were treated with varying doses(100,250 and 400 mg/kg)of P.amarus crude ethanol leaf extract orally for 4 days,and another group was treated with standard drug,artemether and lumefantrine(Lonart®DS).Antiplasmodial activity,seminal quality,some biochemical indices(neutral毩-glucosidase,fructose,and citric acid)in seminal plasma and seminal antioxidant markers(catalase,glutathione peroxidase,reduced glutathione,malondialdehyde,total antioxidant capacity,and acid phosphates)were determined.The mice were euthanized 3 days post treatment and semen was collected from the caudal epididymis and processed for analysis using documented methods and procedures.Results:Malarial infection led to oxidative stress,causing a significant decline in seminal quality(P<0.05).However,treatment with P.amarus crude ethanol leaf extract alleviated oxidative stress and significantly improved seminal quality.The improvement was dose-dependent and compared well with the standard drug,artemether and lumefantrine(Lonart®DS)treatment.Conclusions:The ethanol leaf extracts of P.amarus alleviate male reproductive capacity during malaria infection in murine model by enhancing antioxidant activities.展开更多
Using highly synchronous cultures of Plasmodium falciparum in vitro,the susceptibi- lity of the different stages of the intraerythrocytic parasites to Qinghaosu (QHS) was assessed.The anti- parasitic effect of QHS was...Using highly synchronous cultures of Plasmodium falciparum in vitro,the susceptibi- lity of the different stages of the intraerythrocytic parasites to Qinghaosu (QHS) was assessed.The anti- parasitic effect of QHS was measured by comparing the changes of irradiation of^3 H-hypoxanthine in- corporated into the nucleic acids of parasites exposed to various concentrations of QHS at different stages of growth.It was found that the trophozoite stage of the parasite was the most sensitive to QHS, whereas the early ring stage was the least sensitive,and the sensitivities of the late ring and schizont stages fell between those of the early ring and trophozoite stages.The results revealed the correlation of stage-dependent effects of QHS with the blockade of the protein metabolism of the parasite.展开更多
Objective Sulfanilamide,sulfadiazine,and dapsone were the first sulfonamides to be used to treat malaria by disrupting the folate biosynthesis process,which is essential for parasite survival.Therefore,we aimed to syn...Objective Sulfanilamide,sulfadiazine,and dapsone were the first sulfonamides to be used to treat malaria by disrupting the folate biosynthesis process,which is essential for parasite survival.Therefore,we aimed to synthesize novel N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives through a rational drug design approach.Methods All compounds were synthesized by the conventional method,and the products were characterized by spectral analysis(1 H NMR and mass spectrometry).The progression of the reaction was monitored using thin-layer chromatography(TLC).All the derivatives were analyzed for their effective binding mode in the allosteric site of the plasmodium cysteine protease falcipain-2.Antibacterial and antifungal activities were determined using the broth dilution method.Results S6(N-(2-thiazol-4 yl)-acetyl-aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide and S9(N-(1 H-benzo[d]imidazol-2-yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide formed five hydrogen bonds;S8(N-(2-1 H-imidazol-2 yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide and S10(N-(1 H-benzo[d]imidazol-5-yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide formed four hydrogen bonds with the allosteric site of the enzyme.Considering the docking scores and formation of hydrogen bonds with the target enzyme,the novel derivatives were processed for wet lab synthesis.All the newly synthesized derivatives were subjected to in vitro antimalarial,antifungal,and antibacterial activities.All the derivatives exhibited sufficient sensitivity to the Plasmodium falciparum strain compared to the standards.Moreover,compounds S9 and S10 showed the most potent dual antimicrobial and antimalarial activities.They also exhibited powerful molecular interactions in molecular docking studies.Conclusion Based on the above results,it was concluded that N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives have excellent biological potential to act as antimalarial,antifungal,and antibacterial agents.展开更多
India reports the highest number of malaria cases in Southeast Asia,of which Plasmodium falciparum contribute more than half of the cases every year.North eastern states of India contribute only 3.96%of country’s pop...India reports the highest number of malaria cases in Southeast Asia,of which Plasmodium falciparum contribute more than half of the cases every year.North eastern states of India contribute only 3.96%of country’s population but account for】10%of total reported malaria cases.11%of Plasmodium falciparum cases and 20%of malaria related deaths annually.In India,chloroquine resistance was reported for the first time from northeast region and since then chloroquine treatment failure is being reported from many parts of the region.Increased chloroquine treatment failure has led to change of the drug policy to artemisinin combination therapy as first line of malaria treatment in the region.However,replacing chloroquine to artemisinin combination therapy has not shown significant difference in the overall malaria incidence in the region,The present review addresses the current malaria situation of northeastern region of India in the light of antimalarials drug resistance.展开更多
OBJECTIVE： Phytochemical constituents as well as antimalarial and toxicity potentials of the methanolic extract of the husk fi bre of Dwarf Red variety of Cocos nucifera were evaluated in this study.METHODS： The dri...OBJECTIVE： Phytochemical constituents as well as antimalarial and toxicity potentials of the methanolic extract of the husk fi bre of Dwarf Red variety of Cocos nucifera were evaluated in this study.METHODS： The dried powdered husk fi bre was exhaustively extracted with hexane, ethyl acetate and methanol successively and the methanolic extract was screened for fl avonoids, phenolics, tannins, alkaloids, steroids, triterpenes, phlobatannins, anthraquinones and glycosides. A 4-day suppressive antimalarial test was carried out using Plasmodium berghei NK65-infected mice, to which the extract was administered at doses of 31.25, 62.5, 125, 250 and 500 mg/kg body weight（BW）. Toxicity of the extract was evaluated in rats using selected hematological parameters and organ function indices after orally administering doses of 25, 50 and 100 mg/kg BW for 14 d.RESULTS： Phytochemical analysis revealed the presence of alkaloids, tannins, phenolics, saponins, glycosides, steroids and anthraquinones in the extract. Moreover, the extract reduced parasitemia by 39.2% and 45.8% at doses of 250 and 500 mg/kg BW respectively on day 8 post-inoculation. Various hematological parameters evaluated were not significantly altered（P〉0.05） at all doses of the extract, except red blood cell count which was signifi cantly elevated（P〈0.05） at 100 mg/kg BW. The extract significantly increased（P〈0.05） urea, creatinine, cholesterol, high-density lipoprotein-cholesterol and bilirubin concentrations in the serum as well as atherogenic index, while it reduced albumin concentration significantly（P〈0.05） at higher doses compared to the controls. Alanine aminotransferase activity was reduced in the liver and heart signifi cantly（P〈0.05） but was increased in the serum signifi cantly（P〈0.05） at higher doses of the extract compared to the controls.CONCLUSION： The results suggest that methanolic extract of the Dwarf red variety has partial antimalarial activity at higher doses, but is capable of impairing normal kidney and liver function as well as predisposing subjects to cardiovascular diseases.展开更多
Background: Malaria remains a major cause of morbidity and mortality in Zambia, affecting all levels of society, with children under the age of five and pregnant women being most at risk of serious illness. The availa...Background: Malaria remains a major cause of morbidity and mortality in Zambia, affecting all levels of society, with children under the age of five and pregnant women being most at risk of serious illness. The availability of antimalarial medicines is one of the key interventions of malaria management. This study assessed the availability of antimalarial medicines in community pharmacies in Lusaka district, Zambia. Materials and Methods: This was a cross-sectional study that was conducted among 210 community pharmacies from September to November 2022 using a well-structured checklist in selected areas of Lusaka district. The availability was verified by a physical check of the product. The checklist contained the medicines listed both in the guidelines for diagnosis and treatment of malaria in Zambia as well as in the World Health Organization (WHO) malaria treatment guidelines. Results: This study found that all antimalarials listed in the local treatment guidelines for malaria were available in community pharmacies, though with the varying distribution. Of the 210 community pharmacies, 209 (99.5%) had artemether/lumefantrine in stock. The lowest available antimalarial was quinine/clindamycin, which was only available in 3 (1.4%) of the outlets. Conversely, 3 out of 16 (18.8%) antimalarials that were available in community pharmacies were not listed in the local treatment guidelines of malaria in Zambia, despite being listed in the WHO malaria treatment guidelines. This translated into a compliance level of 81.2% based on the local malaria treatment guidelines. Conclusion: This study concluded that antimalarials were available for all categories of malaria management in community pharmacies, though with a varying distribution. The presence of antimalarials not listed in the Zambian treatment guidelines is of public health concern which may have an impact on antimicrobial resistance in the future.展开更多
Malaria is a ubiquitous tropical disease which occurs by the bite of malaria parasite of genus Plasmodium spp.The procurement and treatment of malaria depend on the cost and emergence of drug resistance,chemical compo...Malaria is a ubiquitous tropical disease which occurs by the bite of malaria parasite of genus Plasmodium spp.The procurement and treatment of malaria depend on the cost and emergence of drug resistance,chemical compositions of drug molecules,and different complications and toxic effects associated with them.The antimalarials are classified as gametocidal,prophylaxis,blood schizonticides,tissue schizonticides and sporontocides.In addition,new antimalarial drugs have been discussed in the present review that offers the advantage singly or in combination with other drugs.The ridiculous vector control methods,appearance of drug-resistant parasites,and deficiency of effective vaccines against malaria are the main aspects responsible for the expansion of malaria.Hence,the development of a new drug is the need of hour to conquer the clinical failures of traditional chemotherapy.Though,the discovery and development of a new drug is a costly and lengthy process,hence different nanotechnological techniques may recommend hopeful approaches for the procurement of malaria amid minimum side effects.Delivery of traditional anti-malarial drugs in nanoform offers an opportunity to improve their therapeutic efficacy,reduced side-effects by targeted delivery and improved patient's compliance.This review article will critically highlight the different traditional,hybrid and new anti-malarial drugs.Moreover,different nanocarriers discovered for the site specific liberation of antimalarials to enhance the therapeutic efficiency of these drugs have been comprehensively discussed in this review.展开更多
文摘Aurein is a cationic antimicrobial peptide, rich in phenylalanine residues. Although the peptide has been extensively studied, its mechanism of action is not fully understood and has not been established. This project is focused on studying the interactions of aurein with model biological membranes and antimalarials using Fourier Transform Infrared (FTIR), fluorescence, dynamic light scattering (DLS), atomic force microscopy (AFM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) techniques. FTIR data revealed conformational changes to the secondary structure of the peptide in the presence of the model membranes. The strongest interactions of aurein were found with DOPC and lipid raft systems. Fluorescence data revealed some differences in the mechanism of interaction between aurein and lipid rafts. Topographical analysis was performed using atomic force microscopy (AFM). AFM images of the peptide with its lipid rafts showed a change in surface roughness suggesting a different mechanism of interaction. DLS data in agreement with FTIR confirmed that aurein interacts differently with the lipid rafts. The results gathered from this study provided new insights on the interaction of aurein. On the other hand, drug-drug interaction issues continue to present a major dilemma for the clinician caring for complex patients such as those infected with infectious disease. This study has examined the interaction of aurein with quinine, primaquine, and chloroquine. Significant interactions between aurein and antimalarials occured at a higher concentration of antimalarials. Interactions between aurein and anti-malarials reveal a strong interaction between aurein and primaquine. Interactions between aurein and quinine or chloroquine were found to be weak and negligible. FTIR, TGA, and DSC may be used in a complementary way to gain insights into the possible drug-drug interactions involving aurein. These studies are needed to initiate in vivo controlled interaction studies between antibiotics and antimalarials.
文摘The triterpene quassinoid ailanthinone is a structurally intricate natural product possessing highly potent antimalarial activity against multidrug resistance plasmodium parasites. Although the mechanism of action of ailanthinone is not completely understood, it is presumed to disrupt regular ribosomal functions by inhibiting parasite protein synthesis. Natural scarcity and low solubility of many quassinoids have impeded their development as potential clinical candidates, but exquisite potency of ailanthinone against Plasmodium remains compelling in the global fight against malaria. Herein, we report the highly selective synthesis of 1-hydroxyl derivatives of ailanthinone, including ester, carbonate, carbamate and sulfonate derivatives. The key feature of the synthesis is a one-step regioselective modification of the 1-hydroxyl group in favor of two other hydroxyl groups at C12 and C13. Derivatives were obtained via direct reaction with acyl/sulfonyl chlorides in the presence of a tertiary amine base without any protection-deprotection. In vitro antimalarial evaluations of these derivatives were compared with chloroquine and mefloquine against the Plasmodium falciparum clones, D6, W2, and TM91C235. The results demonstrate that modification of the 1-hydroxyl group is achievable, and the antimalarial activity of these derivatives relative to the parent product is significantly retained, thus paving the way for synthesis of derivatives with improved biological availability and/or increased potency.
文摘Mice are considered to be a similar model to humans in the pathogenesis of malaria. This study evaluates the effect of parenteral antimalarials on the spleen and liver of Swiss albino mice after chronic exposure to Plasmodium berghei. After chronic exposure to P. berghei NK65 strain, the level of parasitemia was assessed.The mice were treated for 3 days using chloroquine(5 mg/kg), quinine(10 mg/kg),and artemether(2 mg/kg). The effect of chronic exposure and the pattern of recovery were evaluated. There was significant decrease in total body weight after chronic exposure to P. berghei(P < 0.05). An increase in total weight recovery was seen after day 15 of treatment with the antimalarials; this was more pronounced with artemether. A significant increase in liver and spleen weights due to P. berghei infection was seen. There was a recovery pattern due to decrease in liver and spleen weights following antimalarial administration, which was greatest with artemether(P < 0.05). Significant changes were more in parasitized, quinine and artemether groups(P < 0.05). There was a significant decrease in total spleen protein due to chloroquine but a decrease due to quinine and artemether(P < 0.05). No significant changes in liver and spleen albumin were observed after treatment. The highest parasite clearance was observed with artemether, followed by quinine. Five mice died after chronic exposure in all the groups prior to treatment. There was significant enlargement and discoloration of spleen and liver after chronic exposure. This study showed that artemether aided recovery of the liver and spleen better than quinine and chloroquine in albino mice after chronic exposure to P. berghei. This suggests there is potential for improvement in antimalarial therapy.
文摘Malaria is a parasitic disease caused by the bite of female Anopheles mosquito and particularly affects the tropical areas of the world. According to national statistics it is the leading cause of consultations and hospitalizations. Nowadays, despite the surveillance systems for efficient malaria control and access to generic drugs, Benin is witnessing an increased development of illicit drug markets with a large part of the population going towards such markets. However, this is not without adverse impact on the health of individuals, as well as, the economic status of the country. Therefore, the situation needs to be seriously considered by policy makers at various levels, health professionals but also the entire international community in order to thwart this scourge.Regarding the aforementioned situation, the current study was undertaken aiming to perform a quality control of selected antimalarial drugs of the illegal market in Porto-Novo city. Therefore, 40 antimalarial batches were randomly collected in the illicit drug market and submitted to analytical tests such as: macroscopic examination (a visual and critical examination);mass uniformity test;disintegration test;identification test and active ingredients’ content measurement. At the end of the study, the percentages of non-compliance is 97.5%, 5%, 15% and 27.5%, respectively for the content uniformity tests, disintegration, identification and assay. Over-all, 42.5% of noncompliance was recorded. The findings of this study prove that street vended drugs offer no guarantee of good quality and pose a threat to the health of populations. Also, the rate of non-compliance denotes a flaw in the security of the drug distribution system.
文摘Dear Editor,We present the reported case of rapid onset bull’s eye maculopathy.Chloroquine(CQ)and its safer,more widely used analogue,hydroxychloroquine(HCQ),were originally developed as antimalarial medications.However,they have since become essential in the treatment of various autoimmune disorders due to their anti-inflammatory and immunomodulatory properties.HCQ is also being investigated for potential applications in diabetes mellitus,coronavirus disease 2019,heart disease,and as an adjunct in cancer therapy^([1-2]).
基金supported by the National Natural Science Foundation of China(81622042,81773567 and 31771455)National Key R&D Program of China(2018YFA0507300,2018ZX09711001,2020YFE0202200)+1 种基金Innovation Capacity Building Project of Jiangsu province(BM2020019)Shanghai Post-doctoral Excellence Program(2020469)
文摘Malaria still threatens global health seriously today.While the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors,multi-targeting inhibitors are highly desired to overcome the increasingly serious drug resistance.Here,we performed a structure-based drug design on mitochondrial respiratory chain of Plasmodium falciparum and identified an extremely potent molecule,RYL-581,which binds to multiple protein binding sites of P.falciparum simultaneously(allosteric site of type Ⅱ NADH dehydrogenase,Q_(o) and Q_(i) sites of cytochrome bc_(1)).Antimalarials with such multiple targeting mechanism of action have never been reported before.RYL-581 kills various drug-resistant strains in vitro and shows good solubility as well as in vivo activity.This structurebased strategy for designing RYL-581 from starting compound may be helpful for other medicinal chemistry projects in the future,especially for drug discovery on membrane-associated targets.
文摘Objective:To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain(Pf3D7),its clinical isolate(Pf140/SS),and Plasmodium berghei ANKA(PbA).Methods:Using ring-stage survival assay,phenotypic assessments,and SYBR-green-based fluorescence assay,the antimalarial activities of noscapine were assessed compared with dihydroartemisinin(DHA)in in vivo and in vitro studies.In addition,hemolysis and cytotoxicity tests were carried out to evaluate its safety.RT-PCR assay was also conducted to determine the effect of noscapine on papain-like cysteine protease Plasmodium falciparum falcipain-2(PfFP-2).Results:The antimalarial efficacy of noscapine against Pf3D7 and Pf140/SS was comparable to DHA,with IC50 values of(7.68±0.88)and(5.57±0.74)nM/mL,respectively,and>95%inhibition of PbA infected rats.Noscapine also showed a safe profile,as evidenced by low hemolysis and cytotoxicity even at high concentrations.Moreover,PfFP-2 expression was significantly inhibited in both noscapine-treated Pf3D7 and Pf140/SS(P<0.01).Conclusions:Noscapine has antimalarial properties comparable to standard antimalarial DHA with better safety profiles,which may be further explored as a therapeutic candidate for the treatment of malaria.
文摘This review provides a comprehensive overview of the phytochemistry, medicinal properties, and biological activities of the Artemisia species. Artemisia species exhibit a wide range of morphological and phytochemical diversity, showing promise for the treatment of various diseases in humans, plants, and animals. Phytochemicals found in Artemisia spp. include terpenoids, flavonoids, coumarins, caffeoylquinic acids, sterols, and acetylenes. Dietary flavonoids have been linked to reduced cell aging, lipid peroxidation, and cancer risks. Sterols, including plant sterols, play a significant role in reducing the plasma cholesterol levels. Essential oils from Artemisia plants contain volatile chemicals with antibacterial, antiviral, and antifungal properties that contribute to their biological activity. This study aimed to elucidate the effective compounds of Artemisia plants and their medicinal benefits and biological activities.
基金Supported by The Bill and Melinda Gates Foundation support to PATH for the Malaria Control Evaluation Partnership for Africa(MACEPA)project,Grant Number:OPP1013468
文摘Objective:To establish the appropriateness of malaria case management at health facility level in four districts in Zambia.Methods:This study was a retrospective evaluation of the quality of malaria case management at health facilities in four districts conveniently sampled to represent both urban and rural settings in different epidemiological zones and health facility coverage.The review period was from January to December 2008.The sample included twelve lower level health facilities from four districts.The Pearson Chi-square test was used to identify characteristics which affected the quality of case management.Results:Out of 4891 suspected malaria cases recorded at the 12 health facilities,more than 80%of the patients had a temperature taken to establish their fever status.About 67%(CI_(95)66.1-68.7)were tested for parasitemia by either rapid diagnostic test or microscopy,whereas the remaining22.5%(CI_(95)213.1-23.7)were not subjected to any malaria test.Of the 2247 malaria cases reported(complicated and uncomplicated),71%were parasitologicaily confirmed while 29%were clinically diagnosed(unconfirmed).About 56%.(CI_(95)53.9-58.1)of the malaria cases reported were treated with artemether-lumefantrine(AL),35%(CI_(95)33.1-37.0)with sulphadoxine-pyrimethamine,8%(CI_(95)6.9-9.2)with quinine and 1%did not receive any anti-malarial.Approximately 30%of patients WHO were found negative for malaria parasites were still prescribed an anti-malarial,contrary to the guidelines.There were marked inter-district variations in the proportion of patients in WHOm a diagnostic tool was used,and in the choice of anti-malarials for the treatment of malaria confirmed cases.Association between health worker characteristics and quality of case malaria management showed that nurses performed better than environmental health technicians and clinical officers on the decision whether to use the rapid diagnostic test or not.Gender,in service training on malaria,years of residence in the district and length of service of the health worker at the facility were not associated with diagnostic and treatment choices.Conclusions:Malaria case management was characterised by poor adherence to treatment guidelines.The non-adherence was mainly in leans of:inconsistent use of confirmatory tests(rapid diagnostic test or microscopy)for malaria;prescribing anti-malarials which are not recommended(e.g.sulphadoxine-pyrimethamine)and prescribing anti-malarials to cases testing negative.Innovative approaches are required to improve health worker adherence to diagnosis and treatment guidelines.
文摘Objective:To evaluate the antiplasmodial activity of Phyllanthus(P.)amarus crude ethanol leaf extract and its effects on semen quality in male BALB/c mice.Methods:A total of 36 adult mice were divided into six groups,with 6 mice each.Five groups were infected with Plasmodium(P.)berghei,and one group was left uninfeceted.Of the five infected groups,one group was left untreated,three groups were treated with varying doses(100,250 and 400 mg/kg)of P.amarus crude ethanol leaf extract orally for 4 days,and another group was treated with standard drug,artemether and lumefantrine(Lonart®DS).Antiplasmodial activity,seminal quality,some biochemical indices(neutral毩-glucosidase,fructose,and citric acid)in seminal plasma and seminal antioxidant markers(catalase,glutathione peroxidase,reduced glutathione,malondialdehyde,total antioxidant capacity,and acid phosphates)were determined.The mice were euthanized 3 days post treatment and semen was collected from the caudal epididymis and processed for analysis using documented methods and procedures.Results:Malarial infection led to oxidative stress,causing a significant decline in seminal quality(P<0.05).However,treatment with P.amarus crude ethanol leaf extract alleviated oxidative stress and significantly improved seminal quality.The improvement was dose-dependent and compared well with the standard drug,artemether and lumefantrine(Lonart®DS)treatment.Conclusions:The ethanol leaf extracts of P.amarus alleviate male reproductive capacity during malaria infection in murine model by enhancing antioxidant activities.
文摘Using highly synchronous cultures of Plasmodium falciparum in vitro,the susceptibi- lity of the different stages of the intraerythrocytic parasites to Qinghaosu (QHS) was assessed.The anti- parasitic effect of QHS was measured by comparing the changes of irradiation of^3 H-hypoxanthine in- corporated into the nucleic acids of parasites exposed to various concentrations of QHS at different stages of growth.It was found that the trophozoite stage of the parasite was the most sensitive to QHS, whereas the early ring stage was the least sensitive,and the sensitivities of the late ring and schizont stages fell between those of the early ring and trophozoite stages.The results revealed the correlation of stage-dependent effects of QHS with the blockade of the protein metabolism of the parasite.
基金funding support from the National Natural Science Foundation of China(No.82074251)the Hunan Natural Science Foundation of China(No.2018JJ2413)the Hunan Provincial Health and Health Commission Project(No.c2018032)。
文摘Objective Sulfanilamide,sulfadiazine,and dapsone were the first sulfonamides to be used to treat malaria by disrupting the folate biosynthesis process,which is essential for parasite survival.Therefore,we aimed to synthesize novel N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives through a rational drug design approach.Methods All compounds were synthesized by the conventional method,and the products were characterized by spectral analysis(1 H NMR and mass spectrometry).The progression of the reaction was monitored using thin-layer chromatography(TLC).All the derivatives were analyzed for their effective binding mode in the allosteric site of the plasmodium cysteine protease falcipain-2.Antibacterial and antifungal activities were determined using the broth dilution method.Results S6(N-(2-thiazol-4 yl)-acetyl-aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide and S9(N-(1 H-benzo[d]imidazol-2-yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide formed five hydrogen bonds;S8(N-(2-1 H-imidazol-2 yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide and S10(N-(1 H-benzo[d]imidazol-5-yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide formed four hydrogen bonds with the allosteric site of the enzyme.Considering the docking scores and formation of hydrogen bonds with the target enzyme,the novel derivatives were processed for wet lab synthesis.All the newly synthesized derivatives were subjected to in vitro antimalarial,antifungal,and antibacterial activities.All the derivatives exhibited sufficient sensitivity to the Plasmodium falciparum strain compared to the standards.Moreover,compounds S9 and S10 showed the most potent dual antimicrobial and antimalarial activities.They also exhibited powerful molecular interactions in molecular docking studies.Conclusion Based on the above results,it was concluded that N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives have excellent biological potential to act as antimalarial,antifungal,and antibacterial agents.
文摘India reports the highest number of malaria cases in Southeast Asia,of which Plasmodium falciparum contribute more than half of the cases every year.North eastern states of India contribute only 3.96%of country’s population but account for】10%of total reported malaria cases.11%of Plasmodium falciparum cases and 20%of malaria related deaths annually.In India,chloroquine resistance was reported for the first time from northeast region and since then chloroquine treatment failure is being reported from many parts of the region.Increased chloroquine treatment failure has led to change of the drug policy to artemisinin combination therapy as first line of malaria treatment in the region.However,replacing chloroquine to artemisinin combination therapy has not shown significant difference in the overall malaria incidence in the region,The present review addresses the current malaria situation of northeastern region of India in the light of antimalarials drug resistance.
基金supported by the University of Ilorin Central-Based Senate Research Grant (2010)
文摘OBJECTIVE： Phytochemical constituents as well as antimalarial and toxicity potentials of the methanolic extract of the husk fi bre of Dwarf Red variety of Cocos nucifera were evaluated in this study.METHODS： The dried powdered husk fi bre was exhaustively extracted with hexane, ethyl acetate and methanol successively and the methanolic extract was screened for fl avonoids, phenolics, tannins, alkaloids, steroids, triterpenes, phlobatannins, anthraquinones and glycosides. A 4-day suppressive antimalarial test was carried out using Plasmodium berghei NK65-infected mice, to which the extract was administered at doses of 31.25, 62.5, 125, 250 and 500 mg/kg body weight（BW）. Toxicity of the extract was evaluated in rats using selected hematological parameters and organ function indices after orally administering doses of 25, 50 and 100 mg/kg BW for 14 d.RESULTS： Phytochemical analysis revealed the presence of alkaloids, tannins, phenolics, saponins, glycosides, steroids and anthraquinones in the extract. Moreover, the extract reduced parasitemia by 39.2% and 45.8% at doses of 250 and 500 mg/kg BW respectively on day 8 post-inoculation. Various hematological parameters evaluated were not significantly altered（P〉0.05） at all doses of the extract, except red blood cell count which was signifi cantly elevated（P〈0.05） at 100 mg/kg BW. The extract significantly increased（P〈0.05） urea, creatinine, cholesterol, high-density lipoprotein-cholesterol and bilirubin concentrations in the serum as well as atherogenic index, while it reduced albumin concentration significantly（P〈0.05） at higher doses compared to the controls. Alanine aminotransferase activity was reduced in the liver and heart signifi cantly（P〈0.05） but was increased in the serum signifi cantly（P〈0.05） at higher doses of the extract compared to the controls.CONCLUSION： The results suggest that methanolic extract of the Dwarf red variety has partial antimalarial activity at higher doses, but is capable of impairing normal kidney and liver function as well as predisposing subjects to cardiovascular diseases.
文摘Background: Malaria remains a major cause of morbidity and mortality in Zambia, affecting all levels of society, with children under the age of five and pregnant women being most at risk of serious illness. The availability of antimalarial medicines is one of the key interventions of malaria management. This study assessed the availability of antimalarial medicines in community pharmacies in Lusaka district, Zambia. Materials and Methods: This was a cross-sectional study that was conducted among 210 community pharmacies from September to November 2022 using a well-structured checklist in selected areas of Lusaka district. The availability was verified by a physical check of the product. The checklist contained the medicines listed both in the guidelines for diagnosis and treatment of malaria in Zambia as well as in the World Health Organization (WHO) malaria treatment guidelines. Results: This study found that all antimalarials listed in the local treatment guidelines for malaria were available in community pharmacies, though with the varying distribution. Of the 210 community pharmacies, 209 (99.5%) had artemether/lumefantrine in stock. The lowest available antimalarial was quinine/clindamycin, which was only available in 3 (1.4%) of the outlets. Conversely, 3 out of 16 (18.8%) antimalarials that were available in community pharmacies were not listed in the local treatment guidelines of malaria in Zambia, despite being listed in the WHO malaria treatment guidelines. This translated into a compliance level of 81.2% based on the local malaria treatment guidelines. Conclusion: This study concluded that antimalarials were available for all categories of malaria management in community pharmacies, though with a varying distribution. The presence of antimalarials not listed in the Zambian treatment guidelines is of public health concern which may have an impact on antimicrobial resistance in the future.
文摘Malaria is a ubiquitous tropical disease which occurs by the bite of malaria parasite of genus Plasmodium spp.The procurement and treatment of malaria depend on the cost and emergence of drug resistance,chemical compositions of drug molecules,and different complications and toxic effects associated with them.The antimalarials are classified as gametocidal,prophylaxis,blood schizonticides,tissue schizonticides and sporontocides.In addition,new antimalarial drugs have been discussed in the present review that offers the advantage singly or in combination with other drugs.The ridiculous vector control methods,appearance of drug-resistant parasites,and deficiency of effective vaccines against malaria are the main aspects responsible for the expansion of malaria.Hence,the development of a new drug is the need of hour to conquer the clinical failures of traditional chemotherapy.Though,the discovery and development of a new drug is a costly and lengthy process,hence different nanotechnological techniques may recommend hopeful approaches for the procurement of malaria amid minimum side effects.Delivery of traditional anti-malarial drugs in nanoform offers an opportunity to improve their therapeutic efficacy,reduced side-effects by targeted delivery and improved patient's compliance.This review article will critically highlight the different traditional,hybrid and new anti-malarial drugs.Moreover,different nanocarriers discovered for the site specific liberation of antimalarials to enhance the therapeutic efficiency of these drugs have been comprehensively discussed in this review.
