Objective:To isolate the multiple drug resistance(MDR) Mycobacterium tuberculosis(M. tuberculosis) and to screen for the bioactive compounds extracted from marine microalgae. Methods:Sixty seven collected samples that...Objective:To isolate the multiple drug resistance(MDR) Mycobacterium tuberculosis(M. tuberculosis) and to screen for the bioactive compounds extracted from marine microalgae. Methods:Sixty seven collected samples that were confirmed by 16S rDNA analysis as positive with M.tuberculosis infection were subjected to sensitivity test against commercially used front line and second line drugs by absolute concentration method using LJ slants.Seven bacterial isolates numbered I-78,I-101,I-127,I-173,I-202,I-262,I-327 showed resistant for more than 3 drugs were considered as MDR M.tuberculosis.Thus the percentage of 10.4 were recorded MDR-TB. Fifteen marine micro algal extracts were screened for antimycobacterial activity and partial characterization of the active principles was done.Results:The percentage contribution of marine micro algal species on the extraction of antimycobacterials indicated Isochrysis galbana(I. galbana) contain rich bioactive compounds and accounted for 60%inhibition of the total isolates. The percentage contribution of solvents on the extraction of antimicrobials from I.galbana showed that the methanol,chloroform,n-Butanol showed maximum of extraction.The purified eluted compounds(R,0.43) from TLC plate were chromatographed by gas chromatography.The eluted sterol compounds showed 13 unsaturated sterols with 3 major sterols.Conclusions:The present study indicates the presence of unsaturated fatty acids may have the effect on MDR M. tuberculosis,indicating a potential natural alternative to antibiotics.展开更多
Objective: To evaluate the susceptibility of Mycobacterium aurum and Mycobacterium smegmatis in vitro to the essential oils obtained from two medicinal plants: Thymus satureioides(T. satureioides) and Mentha pulegium(...Objective: To evaluate the susceptibility of Mycobacterium aurum and Mycobacterium smegmatis in vitro to the essential oils obtained from two medicinal plants: Thymus satureioides(T. satureioides) and Mentha pulegium(M. pulegium), and to study their chemical composition.Methods: The aerial parts of T. satureioides and M. pulegium(leaves and stems) were hydro-distillated using a Clevenger-type apparatus and essential oils were analyzed and identified by gas chromatography-mass spectrometry. Antimycobacterial screening of essential oils was performed on the basis of the inhibition zone diameter by disc diffusion method against two mycobacterial strains whereas the minimal inhibitory concentration and minimal bactericidal concentration were determined by using the micro-dilution method.Results: Chemical analysis of their aerial part's essential oils gave as major compounds,borneol(34.26%), carvacrol(31.21%) and thymol(3.71%) for T. satureioides and R(+)-pulegone(75.48%), carvone(6.66%) and dihydrocarvone(4.64%) for M. pulegium.Thereafter their antimycobacterial effect evaluation, using the micro-dilution method,indicated that minimal inhibitory concentration values of T. satureioides essential oil ranged from 0.062% to 0.015%(v/v) and from 0.125% to 0.031%(v/v) for M. pulegium respectively against Mycobacterium aurum and Mycobacterium smegmatis.Conclusions: It is clearly evident from the results obtained that the Moroccan medicinal plants have great potential to be used as anti-tuberculosis agents. These findings may help scientists to undertake several research projects to discover useful natural product as new anti-tuberculosis drug.展开更多
Tuberculosis(TB) is a communicable disease caused by Mycobacterium tuberculosis(M. tuberculosis). WHO estimated that 10.4 million new(incident) TB cases worldwide in year 2016. The increased prevalence of drug resista...Tuberculosis(TB) is a communicable disease caused by Mycobacterium tuberculosis(M. tuberculosis). WHO estimated that 10.4 million new(incident) TB cases worldwide in year 2016. The increased prevalence of drug resistant strains and side effects associated with the current anti-tubercular drugs make the treatment options more complicated. Hence, there are necessities to identify new drug candidates to fight against various sub-populations of M. tuberculosis with less or no toxicity/side effects and shorter treatment duration. Bacteriocins produced by lactic acid bacteria(LAB) attract attention of researchers because of its "Generally recognized as safe" status. LAB and its bacteriocins possess an effective antimicrobial activity against various bacteria and fungi. Interestingly bacteriocins such as nisin and lacticin 3147 have shown antimycobacterial activity in vitro. As probiotics, LAB plays a vital role in promoting various health benefits including ability to modulate immune response against various infectious diseases. LAB and its metabolic products activate immune system and thereby limiting the M. tuberculosis pathogenesis. The protein and peptide engineering techniques paved the ways to obtain hybrid bacteriocin derivatives from the known peptide sequence of existing bacteriocin. In this review, we focus on the antimycobacterial property and immunomodulatory role of LAB and its metabolic products. Techniques for large scale synthesis of potential bacteriocin with multifunctional activity and enhanced stability are also discussed.展开更多
A series of novel moxifloxacin methylene and ethylene isatin derivatives with remarkable improvement in lipophilicity,compared to the parent moxifloxacin,was designed,synthesized and characterized by 1H NMR,MS and HRM...A series of novel moxifloxacin methylene and ethylene isatin derivatives with remarkable improvement in lipophilicity,compared to the parent moxifloxacin,was designed,synthesized and characterized by 1H NMR,MS and HRMS.These derivatives were initially evaluated for their in vitro antimycobacterial activity against M.smegmatis CMCC 93202.Compounds 3a―3f,5a,5f and 5j were chosen for the further evaluation of their in vitro activity against Mycobacterium tuberculosis(MTB)H37Rv ATCC 27294 and MDR-MTB 09710.All the target com pounds[minimum inhibitory concentration(MIC):0.39―〉16μg/mL]were far more active than rifampin(MIC:2.0―〉256μg/mL),but less active than moxifloxacin(MIC:0.1―1.0μg/mL)against the three tested strains.The most active compounds 3a and 3c were found to be 2―64 fold more potent than isoniazid and rifampin against M.smegmatis CMCC 93202,2 fold more potent than rifampin against MTB H37Rv ATCC 27294,and 16―〉64 fold more potent than ethambutol,isoniazid and rifampin against MDR-MTB 09710.展开更多
In the present study, a novel series of Mannich bases of 3-substituted 5-(pyridin-4-yl)-1,3, 4-oxadiazol-2-thione derivatives were synthesized. Docking study was performed to rationalize the possible interactions betw...In the present study, a novel series of Mannich bases of 3-substituted 5-(pyridin-4-yl)-1,3, 4-oxadiazol-2-thione derivatives were synthesized. Docking study was performed to rationalize the possible interactions between the synthesized com-pounds and active site of 14DM. The test compounds were screened for antimycobacterial activity using Middlebrook 7H9 medium against M. tuberculosis H37Rv (ATCC 27294) as well as Isoniazid (INH) resistant clinical strain. Among the series 5c and 5a are found to be most potent (susceptible) while the compound 5f did not show activity against M. tuberculosis H37Rv (resistant). The SAR study reveals the importance of substitutions at para position for good activity.展开更多
The Phytochemical investigation on MeOH extract on the bark of Aristolochia brasiliensis Mart.&Zucc(Aristolochi-aceae)led to the isolation of major compound(1)as light brown grainy crystals.The compound was identi...The Phytochemical investigation on MeOH extract on the bark of Aristolochia brasiliensis Mart.&Zucc(Aristolochi-aceae)led to the isolation of major compound(1)as light brown grainy crystals.The compound was identified as 1-(4-hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol(higenamine)on the basis of spectroscopic analysis,including 1D and 2D NMR spectroscopy.The compound was evaluated for its antimycobacterial activity against Mycobacterium indicus pranii(MIP),using Galleria mellonella larva as an in vivo infection model.The survival of MIP infected larvae after a single dose treatment of 100 mg/kg body weight of higenamine was 80%after 24 h.Quantitatively the compound exhibited a dose dependent activity,as evidenced by the reduction of colony density from 10^(5) to 10^(3) CFU for test concentrations of 50,100,150 and 200 mg/kg body weight respectively.The IC50 value for higenamine was 161.6 mg/kg body weight as calculated from a calibration curve.Further analysis showed that,a complete inhibition of MIP in the G.mellonella could be achieved at 334 mg/kg body weight.Despite the fact that MIP has been found to be highly resistant against isoniazid(INH)in an in vitro assay model,in this study the microbe was highly susceptible to this standard anti-TB drug.The isolation of higenamine from the genus Aristolochia and the method used to evaluate its in vivo antimycobacterial activity in G.mellonella are herein reported for the first time.展开更多
Seven 2,6-disubstituted N-(2-phenoxy)ethyl imidazo[1,2-a]pyridine-3-carboxamide series containing various amine moieties were designed and synthesized as new anti-TB agents.Many of them show excellent in vitro activit...Seven 2,6-disubstituted N-(2-phenoxy)ethyl imidazo[1,2-a]pyridine-3-carboxamide series containing various amine moieties were designed and synthesized as new anti-TB agents.Many of them show excellent in vitro activity against both drug-sensitive MTB strain H37Rv and two MDR-MTB clinical isolates(MIC:<0.002-0.030 μg/mL).Compounds 2f,5e and 5g display acceptable safety and pharmacokinetic profiles,opening a new direction for further development.展开更多
We report herein the design and synthesis of a series of novel nitrobenzamide derivatives. Results reveal that many of them display considerable in vitro antitubercular activity. Four N-benzyl or N- (pyridine-2-yl)met...We report herein the design and synthesis of a series of novel nitrobenzamide derivatives. Results reveal that many of them display considerable in vitro antitubercular activity. Four N-benzyl or N- (pyridine-2-yl)methyl 3,5-dinitrobenzamides A6, All, Cl and C4 have not only the same excellent MIC values of<0.016 μg/mL against both drug-sensitive MTB strain H37 Rv and two drug-resistant clinical isolates as PBTZ169 and the lead 1, but also acceptable safety indices (SI > 1500), opening a new direction for further development.展开更多
Ternatolide isolated from Radix Ranuncoli Ternati is considered as the active ingredient against Mycobacterium tuberculosis. Herein, tematolide was synthesized in four steps in 32.7% overall yield by using Yamaguchi e...Ternatolide isolated from Radix Ranuncoli Ternati is considered as the active ingredient against Mycobacterium tuberculosis. Herein, tematolide was synthesized in four steps in 32.7% overall yield by using Yamaguchi esterification as the key step, and its antimycobacterial activity was investigated in vitro using a rapid direct susceptibility assay. It was reported that ternatolide killed the Mycobacterium tuberculosis possibly by enhancing the expression of GLS in PBLs indirectly, and our results indicated that tematolide was weakly active against MTB H37Rv ATCC 27294 directly. Therefore, it can be concluded that its mechanism of action was possibly related to the cellular factors.展开更多
In this study Essential oils were used with cumin, cloves, cinnamon, laurel and anis to determine Minimum Inhibitory Concentration (MIC) against Mycobacterium tuberculosis strains. The MICs were determined on M. tuber...In this study Essential oils were used with cumin, cloves, cinnamon, laurel and anis to determine Minimum Inhibitory Concentration (MIC) against Mycobacterium tuberculosis strains. The MICs were determined on M. tuberculosis H37Rv sensitive to all five firstline antituberculosis drugs (streptomycin, isoniazid, rifampicin, ethambutol and pirazinamide), two H37-Rv (CH-8 and CH-15) isoniazid-resistant, two H37Rv (CH-07 and CH-09) rifampicin-resistant, two H37Rv (CH-03 and CH-06) streptomycin-resistant, and two H37Rv (CH-09 and CH-10) ethambutol-resistant using the microplate alamar blue assay. The results obtained showed that the cumin and cinnamon essential oils showed a MIC of 12.5 μg/ml against reference strain H37Rv. The five essential oils used in this study were effective against the isoniazid-resistant variant of H37RV with MIC values in the range 12.5-100 μg/ml, the most potent being the cumin and cin-namon (MIC = 12.5). Similar results were obtained against rifampicin-resistant variant of H37RV with MIC values in the range 12.5-100 μg/ml;the most active ones?in this case were the essential oils of cumin and cloves. The essential oils of anis and laurel were active with MIC value to 100 μg/ml. Clove, cumin, and cinnamon essential oils were active against all strains utilized in this study, with MIC values in the range 6.25 μg/ml to 25 μg/ml.展开更多
Tuberculosis (TB) remains a public health challenge and one of the leading causes of death worldwide. TB is preventable and curable. However, treatment of tuberculosis has continued to be difficult as a result of rapi...Tuberculosis (TB) remains a public health challenge and one of the leading causes of death worldwide. TB is preventable and curable. However, treatment of tuberculosis has continued to be difficult as a result of rapid increase of multidrug and extensively drug resistant strains of Mycobacterium tuberculosis. Medicinal plants have for centuries been traditionally used in treatment of tuberculosis and similar ailments. They possess antimicrobial properties which render them a new hope as a source of novel bioactive leads in the development of antimycobacterial agents. In this study, 2 plant species commonly used traditionally in Uganda for treatment of tuberculosis, Zanthoxylum leprieurii and Rubia cordifolia were screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis strains;pan sensitive MTB H37Rv, Rifampicin resistant TMC 331 strain and two wild strains (one rifampicin resistant and another one rifampicin susceptible). Antimycobacterial activity of aqueous, ethanolic and methanolic plant extracts was determined using Resazurin Microtiter Assay (REMA). Both plant extracts exhibited significant in vitro antimycobacterial activity against all strains of Mycobacterium tuberculosis. Minimum inhibitory concentrations (MIC) of methanolic crude extracts of both plants ranged from 23.4 μg/mL to 187.5 μg/mL. Comparatively, methanol extracts of both plants possessed superior antimycobacterial activity against all Mycobacterium tuberculosis strains. Our findings indicated that both plants exhibited activity against susceptible and resistant strains of Mycobacterium tuberculosis. While antimycobacterial activity of Z. leprieurii confirms results from previous studies, activity of the extracts of R. cordifolia is reported for the first time in East Africa. Further studies aimed at determining the effects of combination of these plant extracts and standard anti-TB drugs should be carried out.展开更多
With the ever-increasing burden of antimicrobial resistance,the demand to introduce countermeasures becomes increasingly critical.The urgency of this need is intensified by the void in antibiotic discovery,with the id...With the ever-increasing burden of antimicrobial resistance,the demand to introduce countermeasures becomes increasingly critical.The urgency of this need is intensified by the void in antibiotic discovery,with the identification of novel compounds declining with time.Of increasing concern is Mycobacterium abscessus,which displays high levels of intrinsic resistance that lead to poor success rates,even after lengthy drug regimens.Research tackling these issues is now focused on the repurposing of preexisting drugs for antimycobacterial use,facilitating the discovery of antimicrobial compounds amidst a crisis where novel antibiotics are sparse.Part of this includes the use of combination treatments,whereby coadministration of synergistic compounds can reduce dose requirements and slow the progression of antimicrobial resistance in the long term.In this review,we will introduce the current therapeutic options for M.abscessus and provide insight into why treatment is so burdensome.We will also compile the current updates within drug repurposing for this pathogen,including the use of unconventional agents such as antimalarial drugs,the repositioning of antitubercu-losis candidates and the repurposing of preexisting antibiotics,including the application of combination regimens.In addition,the in vitro drug screening platforms used in their discovery will be appraised,with the view of highlighting potential future perspectives that may help increase physiological relevance.This review provides a timely appraisal of the future of M.abscessus treatment.展开更多
Rapid emergence and quick evolution of drug-resistant and aggressive mycobacterial strains have resulted in the present antimycobacterial drug crisis and the persistence of tuberculosis as a major public health proble...Rapid emergence and quick evolution of drug-resistant and aggressive mycobacterial strains have resulted in the present antimycobacterial drug crisis and the persistence of tuberculosis as a major public health problem.Green/biological nanotechnologies constitute an interesting area of research for discovering antimycobacterial agents.This review focused on the biological(green)synthesis of silver nanoparticles(AgNPs)as an alternative source of antimycobacterial agents.Data for this study were searched and screened from three electronic databases(Google Scholar,PubMed and ScienceDirect)following the Preferred Reporting Items for Systematic Reviews and Meta-analyses flowchart.Data from in total 17 eligible studieswere reported in this systematic review.Twelve of the 17 studies used plants to fabricate AgNPs,whereas the remaining five studies used microorganisms(bacteria and/or fungi).Silver as part of silver nitrate(AgNO3)was themetal precursor reported for the synthesis of AgNPs in these studies.Silver nanoparticles were mostly spherical,with sizes ranging from12 to140nm.Resultsbasedon minimum inhibitory concentrations varied between studies and were divided into three groups:(i)those more effective than the antibiotic(controls),(ii)those more effective than plant extracts,and(iii)those less effective than the antibiotic controls.In addition,little or no cytotoxicity effects were reported.Silver nanoparticles were also shown to be highly specific or selective toward mycobacterial strains.This systematic review highlights the antimycobacterial potential of biologically synthesized AgNPs,underscoring the possibility of discovering/developing new antimycobacterial agents using biological synthesis approaches with less toxicity and high selectivity.展开更多
Objective:To evaluate antimicrobial and antimycobacterial activity of three seaweeds[Gelidiella acerosa(G.acerosa),Turbinaria conoides(T.conoides)and Sargassum wightii(S.wightii)]from Gulf of Manner.Methods:Three seaw...Objective:To evaluate antimicrobial and antimycobacterial activity of three seaweeds[Gelidiella acerosa(G.acerosa),Turbinaria conoides(T.conoides)and Sargassum wightii(S.wightii)]from Gulf of Manner.Methods:Three seaweeds G.acerosa,T.conoides and S.wightii were collected from Gulf of Mannar,South-East Coast of India.Solvent extraction of the selected seaweeds was done using hexane and ethanol.These extracts were tested for antibacterial activity against four bacterial strains(Escherichia coli,Pseudomonas aeruginosa,Bacillus subtilis and Staphylococcus aureus)by disc diffusion method.The active extracts of T.conoides were tested for antimycobacterial activity by luciferase reporter phage assay at two different concentrations(100μg/mL and 500μg/mL).Results:Among the tested seaweeds,ethanol extract of T.conoides showed maximum antibacterial activity against Bacillus subtilis and Staphylococcus aureus followed by hexane extract at concentration of 1 mg/disc.The remaining two seaweeds(G.acerosa and S.wightii)did not show any activity.The ethanol extract of T.conoides exhibited maximum antimycobacterial activity(87.33%)followed by hexane extract(74.68%)against Mycobacterium tuberculosis H37Rv at 500μg/mL.Conclusions:Ethanol extract of T.conoids showed both antibacterial and antimycobacterial activity.Further photochemical studies are needed to identify the active antimycobacterial agents.展开更多
文摘Objective:To isolate the multiple drug resistance(MDR) Mycobacterium tuberculosis(M. tuberculosis) and to screen for the bioactive compounds extracted from marine microalgae. Methods:Sixty seven collected samples that were confirmed by 16S rDNA analysis as positive with M.tuberculosis infection were subjected to sensitivity test against commercially used front line and second line drugs by absolute concentration method using LJ slants.Seven bacterial isolates numbered I-78,I-101,I-127,I-173,I-202,I-262,I-327 showed resistant for more than 3 drugs were considered as MDR M.tuberculosis.Thus the percentage of 10.4 were recorded MDR-TB. Fifteen marine micro algal extracts were screened for antimycobacterial activity and partial characterization of the active principles was done.Results:The percentage contribution of marine micro algal species on the extraction of antimycobacterials indicated Isochrysis galbana(I. galbana) contain rich bioactive compounds and accounted for 60%inhibition of the total isolates. The percentage contribution of solvents on the extraction of antimicrobials from I.galbana showed that the methanol,chloroform,n-Butanol showed maximum of extraction.The purified eluted compounds(R,0.43) from TLC plate were chromatographed by gas chromatography.The eluted sterol compounds showed 13 unsaturated sterols with 3 major sterols.Conclusions:The present study indicates the presence of unsaturated fatty acids may have the effect on MDR M. tuberculosis,indicating a potential natural alternative to antibiotics.
基金Supported by the Cooperation for Innovation in the Agro-Food Domain Project within the 7th Research and Development Framework Programme FP7-INCO-2013-9(Grant agreement number 609495)
文摘Objective: To evaluate the susceptibility of Mycobacterium aurum and Mycobacterium smegmatis in vitro to the essential oils obtained from two medicinal plants: Thymus satureioides(T. satureioides) and Mentha pulegium(M. pulegium), and to study their chemical composition.Methods: The aerial parts of T. satureioides and M. pulegium(leaves and stems) were hydro-distillated using a Clevenger-type apparatus and essential oils were analyzed and identified by gas chromatography-mass spectrometry. Antimycobacterial screening of essential oils was performed on the basis of the inhibition zone diameter by disc diffusion method against two mycobacterial strains whereas the minimal inhibitory concentration and minimal bactericidal concentration were determined by using the micro-dilution method.Results: Chemical analysis of their aerial part's essential oils gave as major compounds,borneol(34.26%), carvacrol(31.21%) and thymol(3.71%) for T. satureioides and R(+)-pulegone(75.48%), carvone(6.66%) and dihydrocarvone(4.64%) for M. pulegium.Thereafter their antimycobacterial effect evaluation, using the micro-dilution method,indicated that minimal inhibitory concentration values of T. satureioides essential oil ranged from 0.062% to 0.015%(v/v) and from 0.125% to 0.031%(v/v) for M. pulegium respectively against Mycobacterium aurum and Mycobacterium smegmatis.Conclusions: It is clearly evident from the results obtained that the Moroccan medicinal plants have great potential to be used as anti-tuberculosis agents. These findings may help scientists to undertake several research projects to discover useful natural product as new anti-tuberculosis drug.
基金supported by Sathyabama Institute of Science and Technology,Chennai,Tamil Nadu,India and Indian Council of Medical Research(ICMR),New Delhi,India(Ref.No:5/8/5/19/2014-ECD-I)
文摘Tuberculosis(TB) is a communicable disease caused by Mycobacterium tuberculosis(M. tuberculosis). WHO estimated that 10.4 million new(incident) TB cases worldwide in year 2016. The increased prevalence of drug resistant strains and side effects associated with the current anti-tubercular drugs make the treatment options more complicated. Hence, there are necessities to identify new drug candidates to fight against various sub-populations of M. tuberculosis with less or no toxicity/side effects and shorter treatment duration. Bacteriocins produced by lactic acid bacteria(LAB) attract attention of researchers because of its "Generally recognized as safe" status. LAB and its bacteriocins possess an effective antimicrobial activity against various bacteria and fungi. Interestingly bacteriocins such as nisin and lacticin 3147 have shown antimycobacterial activity in vitro. As probiotics, LAB plays a vital role in promoting various health benefits including ability to modulate immune response against various infectious diseases. LAB and its metabolic products activate immune system and thereby limiting the M. tuberculosis pathogenesis. The protein and peptide engineering techniques paved the ways to obtain hybrid bacteriocin derivatives from the known peptide sequence of existing bacteriocin. In this review, we focus on the antimycobacterial property and immunomodulatory role of LAB and its metabolic products. Techniques for large scale synthesis of potential bacteriocin with multifunctional activity and enhanced stability are also discussed.
基金Supported by the National Key Project of Major Infectious Disease of China(No.2008ZX10003-006)the National S&T Major Special Project on Major New Drug Innovation,China(No.2009ZX09301-003)
文摘A series of novel moxifloxacin methylene and ethylene isatin derivatives with remarkable improvement in lipophilicity,compared to the parent moxifloxacin,was designed,synthesized and characterized by 1H NMR,MS and HRMS.These derivatives were initially evaluated for their in vitro antimycobacterial activity against M.smegmatis CMCC 93202.Compounds 3a―3f,5a,5f and 5j were chosen for the further evaluation of their in vitro activity against Mycobacterium tuberculosis(MTB)H37Rv ATCC 27294 and MDR-MTB 09710.All the target com pounds[minimum inhibitory concentration(MIC):0.39―〉16μg/mL]were far more active than rifampin(MIC:2.0―〉256μg/mL),but less active than moxifloxacin(MIC:0.1―1.0μg/mL)against the three tested strains.The most active compounds 3a and 3c were found to be 2―64 fold more potent than isoniazid and rifampin against M.smegmatis CMCC 93202,2 fold more potent than rifampin against MTB H37Rv ATCC 27294,and 16―〉64 fold more potent than ethambutol,isoniazid and rifampin against MDR-MTB 09710.
文摘In the present study, a novel series of Mannich bases of 3-substituted 5-(pyridin-4-yl)-1,3, 4-oxadiazol-2-thione derivatives were synthesized. Docking study was performed to rationalize the possible interactions between the synthesized com-pounds and active site of 14DM. The test compounds were screened for antimycobacterial activity using Middlebrook 7H9 medium against M. tuberculosis H37Rv (ATCC 27294) as well as Isoniazid (INH) resistant clinical strain. Among the series 5c and 5a are found to be most potent (susceptible) while the compound 5f did not show activity against M. tuberculosis H37Rv (resistant). The SAR study reveals the importance of substitutions at para position for good activity.
基金supported by the International Foundation for Science(IFS)Grant Number J/4894-2.
文摘The Phytochemical investigation on MeOH extract on the bark of Aristolochia brasiliensis Mart.&Zucc(Aristolochi-aceae)led to the isolation of major compound(1)as light brown grainy crystals.The compound was identified as 1-(4-hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol(higenamine)on the basis of spectroscopic analysis,including 1D and 2D NMR spectroscopy.The compound was evaluated for its antimycobacterial activity against Mycobacterium indicus pranii(MIP),using Galleria mellonella larva as an in vivo infection model.The survival of MIP infected larvae after a single dose treatment of 100 mg/kg body weight of higenamine was 80%after 24 h.Quantitatively the compound exhibited a dose dependent activity,as evidenced by the reduction of colony density from 10^(5) to 10^(3) CFU for test concentrations of 50,100,150 and 200 mg/kg body weight respectively.The IC50 value for higenamine was 161.6 mg/kg body weight as calculated from a calibration curve.Further analysis showed that,a complete inhibition of MIP in the G.mellonella could be achieved at 334 mg/kg body weight.Despite the fact that MIP has been found to be highly resistant against isoniazid(INH)in an in vitro assay model,in this study the microbe was highly susceptible to this standard anti-TB drug.The isolation of higenamine from the genus Aristolochia and the method used to evaluate its in vivo antimycobacterial activity in G.mellonella are herein reported for the first time.
基金supported by the CAMS Innovation Fund for Medical Science(No.CAMS-2017-I2M-1-011)National Mega-project for Innovative Drugs(Nos.2015ZX09102007-008,2018ZX09721001004-007,2018ZX09711001-007-002)the National Natural Science Foundation of China(No.81872753)。
文摘Seven 2,6-disubstituted N-(2-phenoxy)ethyl imidazo[1,2-a]pyridine-3-carboxamide series containing various amine moieties were designed and synthesized as new anti-TB agents.Many of them show excellent in vitro activity against both drug-sensitive MTB strain H37Rv and two MDR-MTB clinical isolates(MIC:<0.002-0.030 μg/mL).Compounds 2f,5e and 5g display acceptable safety and pharmacokinetic profiles,opening a new direction for further development.
基金supported by the National Mega-project for Innovative Drugs(Nos.2015ZX09102007-008,2015ZX09102007015,2015ZX0 9304006-016,2018ZX09721001-004-007, 2018ZX09711001-007-002)CAMS Initiative for Innovative Medicine(No.2016-I2M-1-010)+1 种基金CAMS Innovation Fund for Medical Science(Nos.CAMS-2016-I2M-1-010,CAMS-2017-I2M-1-011)PUMC Youth Fund (No. 2017350011)
文摘We report herein the design and synthesis of a series of novel nitrobenzamide derivatives. Results reveal that many of them display considerable in vitro antitubercular activity. Four N-benzyl or N- (pyridine-2-yl)methyl 3,5-dinitrobenzamides A6, All, Cl and C4 have not only the same excellent MIC values of<0.016 μg/mL against both drug-sensitive MTB strain H37 Rv and two drug-resistant clinical isolates as PBTZ169 and the lead 1, but also acceptable safety indices (SI > 1500), opening a new direction for further development.
基金National S&T Major Special Project on Major New Drug Innovation (Grant No. 2012ZX09102-101-001)
文摘Ternatolide isolated from Radix Ranuncoli Ternati is considered as the active ingredient against Mycobacterium tuberculosis. Herein, tematolide was synthesized in four steps in 32.7% overall yield by using Yamaguchi esterification as the key step, and its antimycobacterial activity was investigated in vitro using a rapid direct susceptibility assay. It was reported that ternatolide killed the Mycobacterium tuberculosis possibly by enhancing the expression of GLS in PBLs indirectly, and our results indicated that tematolide was weakly active against MTB H37Rv ATCC 27294 directly. Therefore, it can be concluded that its mechanism of action was possibly related to the cellular factors.
文摘In this study Essential oils were used with cumin, cloves, cinnamon, laurel and anis to determine Minimum Inhibitory Concentration (MIC) against Mycobacterium tuberculosis strains. The MICs were determined on M. tuberculosis H37Rv sensitive to all five firstline antituberculosis drugs (streptomycin, isoniazid, rifampicin, ethambutol and pirazinamide), two H37-Rv (CH-8 and CH-15) isoniazid-resistant, two H37Rv (CH-07 and CH-09) rifampicin-resistant, two H37Rv (CH-03 and CH-06) streptomycin-resistant, and two H37Rv (CH-09 and CH-10) ethambutol-resistant using the microplate alamar blue assay. The results obtained showed that the cumin and cinnamon essential oils showed a MIC of 12.5 μg/ml against reference strain H37Rv. The five essential oils used in this study were effective against the isoniazid-resistant variant of H37RV with MIC values in the range 12.5-100 μg/ml, the most potent being the cumin and cin-namon (MIC = 12.5). Similar results were obtained against rifampicin-resistant variant of H37RV with MIC values in the range 12.5-100 μg/ml;the most active ones?in this case were the essential oils of cumin and cloves. The essential oils of anis and laurel were active with MIC value to 100 μg/ml. Clove, cumin, and cinnamon essential oils were active against all strains utilized in this study, with MIC values in the range 6.25 μg/ml to 25 μg/ml.
文摘Tuberculosis (TB) remains a public health challenge and one of the leading causes of death worldwide. TB is preventable and curable. However, treatment of tuberculosis has continued to be difficult as a result of rapid increase of multidrug and extensively drug resistant strains of Mycobacterium tuberculosis. Medicinal plants have for centuries been traditionally used in treatment of tuberculosis and similar ailments. They possess antimicrobial properties which render them a new hope as a source of novel bioactive leads in the development of antimycobacterial agents. In this study, 2 plant species commonly used traditionally in Uganda for treatment of tuberculosis, Zanthoxylum leprieurii and Rubia cordifolia were screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis strains;pan sensitive MTB H37Rv, Rifampicin resistant TMC 331 strain and two wild strains (one rifampicin resistant and another one rifampicin susceptible). Antimycobacterial activity of aqueous, ethanolic and methanolic plant extracts was determined using Resazurin Microtiter Assay (REMA). Both plant extracts exhibited significant in vitro antimycobacterial activity against all strains of Mycobacterium tuberculosis. Minimum inhibitory concentrations (MIC) of methanolic crude extracts of both plants ranged from 23.4 μg/mL to 187.5 μg/mL. Comparatively, methanol extracts of both plants possessed superior antimycobacterial activity against all Mycobacterium tuberculosis strains. Our findings indicated that both plants exhibited activity against susceptible and resistant strains of Mycobacterium tuberculosis. While antimycobacterial activity of Z. leprieurii confirms results from previous studies, activity of the extracts of R. cordifolia is reported for the first time in East Africa. Further studies aimed at determining the effects of combination of these plant extracts and standard anti-TB drugs should be carried out.
基金funded by the Engineering and Physical Sciences Research Council(EPSRC)and Science Foundation Ireland(SFI)Centre for Doctoral Training in Engineered Tissues for Discovery,Industry and Medicine(EP/S02347X/1)EJB is supported by a PhD Studentship funded by LifETIME CDT(EPSRC and SFI)AM is supported by a PhD Studentship jointly funded by LifETIME CDT(EPSRC and SFI)and Sphere Fluidics.
文摘With the ever-increasing burden of antimicrobial resistance,the demand to introduce countermeasures becomes increasingly critical.The urgency of this need is intensified by the void in antibiotic discovery,with the identification of novel compounds declining with time.Of increasing concern is Mycobacterium abscessus,which displays high levels of intrinsic resistance that lead to poor success rates,even after lengthy drug regimens.Research tackling these issues is now focused on the repurposing of preexisting drugs for antimycobacterial use,facilitating the discovery of antimicrobial compounds amidst a crisis where novel antibiotics are sparse.Part of this includes the use of combination treatments,whereby coadministration of synergistic compounds can reduce dose requirements and slow the progression of antimicrobial resistance in the long term.In this review,we will introduce the current therapeutic options for M.abscessus and provide insight into why treatment is so burdensome.We will also compile the current updates within drug repurposing for this pathogen,including the use of unconventional agents such as antimalarial drugs,the repositioning of antitubercu-losis candidates and the repurposing of preexisting antibiotics,including the application of combination regimens.In addition,the in vitro drug screening platforms used in their discovery will be appraised,with the view of highlighting potential future perspectives that may help increase physiological relevance.This review provides a timely appraisal of the future of M.abscessus treatment.
文摘Rapid emergence and quick evolution of drug-resistant and aggressive mycobacterial strains have resulted in the present antimycobacterial drug crisis and the persistence of tuberculosis as a major public health problem.Green/biological nanotechnologies constitute an interesting area of research for discovering antimycobacterial agents.This review focused on the biological(green)synthesis of silver nanoparticles(AgNPs)as an alternative source of antimycobacterial agents.Data for this study were searched and screened from three electronic databases(Google Scholar,PubMed and ScienceDirect)following the Preferred Reporting Items for Systematic Reviews and Meta-analyses flowchart.Data from in total 17 eligible studieswere reported in this systematic review.Twelve of the 17 studies used plants to fabricate AgNPs,whereas the remaining five studies used microorganisms(bacteria and/or fungi).Silver as part of silver nitrate(AgNO3)was themetal precursor reported for the synthesis of AgNPs in these studies.Silver nanoparticles were mostly spherical,with sizes ranging from12 to140nm.Resultsbasedon minimum inhibitory concentrations varied between studies and were divided into three groups:(i)those more effective than the antibiotic(controls),(ii)those more effective than plant extracts,and(iii)those less effective than the antibiotic controls.In addition,little or no cytotoxicity effects were reported.Silver nanoparticles were also shown to be highly specific or selective toward mycobacterial strains.This systematic review highlights the antimycobacterial potential of biologically synthesized AgNPs,underscoring the possibility of discovering/developing new antimycobacterial agents using biological synthesis approaches with less toxicity and high selectivity.
文摘Objective:To evaluate antimicrobial and antimycobacterial activity of three seaweeds[Gelidiella acerosa(G.acerosa),Turbinaria conoides(T.conoides)and Sargassum wightii(S.wightii)]from Gulf of Manner.Methods:Three seaweeds G.acerosa,T.conoides and S.wightii were collected from Gulf of Mannar,South-East Coast of India.Solvent extraction of the selected seaweeds was done using hexane and ethanol.These extracts were tested for antibacterial activity against four bacterial strains(Escherichia coli,Pseudomonas aeruginosa,Bacillus subtilis and Staphylococcus aureus)by disc diffusion method.The active extracts of T.conoides were tested for antimycobacterial activity by luciferase reporter phage assay at two different concentrations(100μg/mL and 500μg/mL).Results:Among the tested seaweeds,ethanol extract of T.conoides showed maximum antibacterial activity against Bacillus subtilis and Staphylococcus aureus followed by hexane extract at concentration of 1 mg/disc.The remaining two seaweeds(G.acerosa and S.wightii)did not show any activity.The ethanol extract of T.conoides exhibited maximum antimycobacterial activity(87.33%)followed by hexane extract(74.68%)against Mycobacterium tuberculosis H37Rv at 500μg/mL.Conclusions:Ethanol extract of T.conoids showed both antibacterial and antimycobacterial activity.Further photochemical studies are needed to identify the active antimycobacterial agents.
