Eight new annonaceous acetogenins, squamotin A–D(1–4), annosquatin IV–V(5 and 6), muricin O(7) and squamosten B(8), together with four known ones(9–12) were isolated from the seeds of Annona squamosa. Their struct...Eight new annonaceous acetogenins, squamotin A–D(1–4), annosquatin IV–V(5 and 6), muricin O(7) and squamosten B(8), together with four known ones(9–12) were isolated from the seeds of Annona squamosa. Their structures were elucidated by chemical methods and spectral data. The inhibitory activities of compound 1–9 against three multidrug resistance cell lines were evaluated. All tested compounds showed strong cytotoxicity.展开更多
Toxic and nutritional effects of annonaceous acetogenins and their semisynthetic analogues on Spodoptera frugiperda were evaluated. Structural modification of the natural ACG, blocking the OH flanking THF with MOM, al...Toxic and nutritional effects of annonaceous acetogenins and their semisynthetic analogues on Spodoptera frugiperda were evaluated. Structural modification of the natural ACG, blocking the OH flanking THF with MOM, allowed us to suggest the mode of action of ACG in the membrane. Our study emphasizes the role of the flanking OH and acetyl groups of THF with the membrane hydrophilic polar head groups. They are essential structural factors in the ACG that facilitate the intermolecular interaction that dehydrates the membrane and makes it potentially toxic against Spodoptera frugiperda.展开更多
Background: Annonaceous acetogenins enclose a large number of biological activities, among which the insecticidal stands out. Methods: We report herein the biocide effects of natural acetogenins from Annona squamosa, ...Background: Annonaceous acetogenins enclose a large number of biological activities, among which the insecticidal stands out. Methods: We report herein the biocide effects of natural acetogenins from Annona squamosa, A.?muricata and A. montana seeds: annonacin, cis-annonacin, cis-annonacin-10- one, asimicin, rolliniastatin-2, cherimolin-1, cherimolin-2, almuñequin, and two β-OH acetogenins: laherradurin and itrabin on Spodoptera frugiperda Smith (Lepidoptera: Noctuidae). Also, some acetylated and methoxy methylated ACG derivatives were synthesized and evaluated: annonacin (3 OAc), annonacin (4 OAc), asimicin (3 OAc), rolliniastatin-2 (3 OAc), rolliniastatin-2 (MOM), laherradurin (3 OAc) and itrabin (3 OAc). Results: The natural acetogenin rolliniastatin-2 (100 μg·g-1 of diet) produced the most important toxic action causing 100% mortality of early instar larvae. Derivatization of ACG yielded compounds that produced nutritional alterations. The incorporation of rolliniastatin-2 (3 OAc) and rolliniastatin-2 (3 MOM) (100 μg·g-1) into the artificial diet of Spodoptera frugiperdadisplayed the strongest antifeedant effects causing marked decreasings in larval growth and adult lethal malformations. Conclusion: Natural acetogenins are promising metabolites for insect control. Derivatization of these compounds reduces their toxicity to early instar larvae.展开更多
Annonaceous acetogenins enclose a large number of biological activities, among which the insecticidal stands out. <em>Spodoptera frugiperda</em> is a pest that affects corn crops among others and has a gre...Annonaceous acetogenins enclose a large number of biological activities, among which the insecticidal stands out. <em>Spodoptera frugiperda</em> is a pest that affects corn crops among others and has a great capacity to develop resistance to traditional insecticides, which represents sufficient reasons for the search for new alternatives for their control. The objective of this study was to determine the appropriate concentration and screening new natural insecticides against second instar larvae of <em>S. frugiperda</em>, under glasshouse conditions on <em>Zea mays</em> L. Natural products such as annonaceous acetogenins and some acetylated and methoxy methylated ACG derivatives and the commercial product Lambda-cyhalotrin (LC) were evaluated. The percent mortalities of <em>S. frugiperda </em>larvae in glasshouse conditions were recorded after 24, 48 and 72 h of treatment application. The results showed that the acetogenins tested were significantly (P < 0.05) different in relation to pest mortality than untreated check. After 72 h of treatment application the highest percent mortalities were obtained with the mixture of two natural products, rolliniastatin-2 (<strong>5</strong>) (100 μg/mL) + squamocin (<strong>6</strong>) (100 μg/mL) + LC (50 μg/mL) that proved the most effective and gave (100%), while rolliniastatin-2 (<strong>5</strong>) at 100 μg/mL alone, gave lowest percent mortality (65%), followed by squamocin (<strong>6</strong>) at 100 μg/mL (55%) and LC at 50 μg/mL (30%). The acetylated and methoxy methylated ACGs derivatives caused very low mortality (25% - 35%). It is recommended the mixture as a management option of <em>S. frugiperda</em> as a component of integrated pest management. The results allow us to infer that the addition of natural ACGs synergizes the insecticidal activity of the commercial product. Finding a new ecological alternative for insect control.展开更多
Annonaceous acetogenins (ACG), belonging to the family Annonaceae, represent a class of bioactive compounds whose toxic effects have been reported for several spe-cies of insects. Given their insecticidal properties, ...Annonaceous acetogenins (ACG), belonging to the family Annonaceae, represent a class of bioactive compounds whose toxic effects have been reported for several spe-cies of insects. Given their insecticidal properties, we first carried out the isolation of the ACG from a Brazilian collection of the seeds of Annona squamosa (Annonaceae) and prepared their methoxy methylated (MOM) and acetylated (OAc) derivatives by chemical methods. ACG analogues were semi-synthesized and characterized by spec-troscopic techniques (<sup>1</sup>H and <sup>13</sup>C-NMR). We isolated ten natural acetogenins: squamo-cin, molvizarin, motrilin, rolliniastatin-2, almunequin, cherimolin-1, cherimolin-2, an-nonacin, squamocin D and asiminecin. The main objective of this study is to report the antifeedant, toxic and nutritional effects of three of those natural acetogenins and their acetylated and methoxy methylated derivatives on Spodoptera frugiperda Smith (Lep-idoptera: Noctuidae). The natural ACGs squamocin and molvizarin killed 100% of S. frugiperda larvae, followed by motrilin (80%). Acetylated derivatives had less toxic and nutritional effects that led to pupal mortality and adult fatal malformations. The addition of MOM derivatives to the larval diet has not toxic effects on larvae, but significantly reduces growth rate and efficiency in conversion of ingested food into biomass, affecting adult survival.展开更多
Two mild-cytotoxic bistetrahydrofuran (THF) ring annonaceous acetogenins named calamistrins F(1) and G(2) were isolated from the ethanolic extract of the roots of U. calamistrata Hance. Their structures including the ...Two mild-cytotoxic bistetrahydrofuran (THF) ring annonaceous acetogenins named calamistrins F(1) and G(2) were isolated from the ethanolic extract of the roots of U. calamistrata Hance. Their structures including the relative and absolute configurations were determined by chemical derivation and spectral analysis. Calamistrins F and G were a pair of epimers at C-26 which both had THF ring from C-18 to C-25 and three OH groups at C-5, C-17 and C-26.展开更多
Objective： To confirm the anticancer effect of total annonaceous acetogenins （TAAs） abstracted from Annona squamosa Linn. on human hepatocarcinoma. Methods： The inhibitory effect of TAAs was demonstrated in H,,-be...Objective： To confirm the anticancer effect of total annonaceous acetogenins （TAAs） abstracted from Annona squamosa Linn. on human hepatocarcinoma. Methods： The inhibitory effect of TAAs was demonstrated in H,,-bearing mice. The potency of TAAs was confirmed as its 50% inhibiting concentration （IC50） on Bel-7402 cell under Sulfur Rhodamine B staining. Both underlying mechanisms were explored as cellular apoptosis and cell cycle under flow cytometry. Mitochondrial and recipient apoptotic pathways were differentiated as mitochondrial membrane potential under flow cytometry and caspases activities under fluorescence analysis. Results： The inhibitory rate of TAAs in mice was 50.98% at 4 mg/kg dose. The IC50 of TAAs on Bel-7402 was 20.06 μg/mL （15.13-26.61 μg/mL）. Effective mechanisms of TAAs were confirmed as both of arresting cell cycle at G1 phase and inducing apoptosis dose- and time-dependently. Mitochondrial and recipient pathways involved in apoptotic actions of TAAs. Conclusion： TAAs is effective for hepatocarcinoma, via inhibiting proliferation and inducing apoptosis.展开更多
A new Annonaceous acetogenin, squamostolide (1), was isolated from the seeds of Annona squamosa. Its structure was elucidated based on spectroscopic methods and comparison with known compounds. It is the first examp...A new Annonaceous acetogenin, squamostolide (1), was isolated from the seeds of Annona squamosa. Its structure was elucidated based on spectroscopic methods and comparison with known compounds. It is the first example of Annonaceous acetogenin with each of the two ends of the aliphatic chain bearing a g-lactone. The new compound exhibited cytotoxic activity in vitro against bel-7402 and CNE2 human tumor cell lines.展开更多
Annona muricata(A.muricata)is a tropical plant species belonging to family Annonaceae and known for its many medicinal uses.This review focuses on the research history of its traditional uses,phytochemicals,pharmacolo...Annona muricata(A.muricata)is a tropical plant species belonging to family Annonaceae and known for its many medicinal uses.This review focuses on the research history of its traditional uses,phytochemicals,pharmacological activities,toxicological aspects of the extracts and isolated compounds,as well as the in vitro propagation studies with the objective of stimulating further studies on this plant for human consumption and treatment.A.muricata extracts have been identified in tropical regions to traditionally treat diverse conditions ranging from fever to diabetes and cancer.More than 200 chemical compounds have been identified and isolated from this plant,the most important being alkaloids,phenols and acetogenins.Using in vitro studies,its extracts and phytochemicals have been characterized as antioxidant,anti-microbial,anti-inflammatory,insecticidal,larvicidal,and cytotoxic to cancer cells.In vivo studies have revealed anxiolytic,antistress,anti-inflammatory,immunomodulatory,antimalarial,antidepressant,gastro protective,wound healing,hepato-protective,hypoglycemic,anticancer and anti-tumoral activities.In silico studies have also been reported.In addition,clinical studies support the hypoglycemic as well as some anticancer activities.Mechanisms of action of some pharmacological activities have been elucidated.However,some phytochemical compounds isolated from A.muricata have shown a neurotoxic effect in vitro and in vivo,and therefore,these crude extracts and isolated compounds need to be further investigated to define the magnitude of the effects,optimal dosage,and mechanisms of action,long-term safety,and potential side effects.Additionally,more clinical studies are necessary to support the therapeutic potential of this plant.Some studies were also found to have successfully regenerated the plant in vitro,but with limited success.The reported toxicity notwithstanding,A.muricata extracts seem to be some of the safest and promising therapeutic agents of the 21st century and beyond that need to be studied further for better medicinal formulations and diseases management.展开更多
Objective: To evaluate the anticancer potentials of Annona muricata fruit by in vitro and in vivo methods. Methods: The ethanolic extract of Annona muricata fruit was prepared by Soxhlet extraction method and further ...Objective: To evaluate the anticancer potentials of Annona muricata fruit by in vitro and in vivo methods. Methods: The ethanolic extract of Annona muricata fruit was prepared by Soxhlet extraction method and further fractionated with petroleum ether, ethyl acetate and chloroform. The fractions were tested for cytotoxicity, apoptosis, scratch wound assay, and cell cycle analysis. IC50, apoptotic index and percentage cell migration were determined using HepG2 cells. For the in vivo studies, hepatocellular carcinoma was induced by administering 0.01% diethylnitrosamine(DEN) in drinking water in Wistar rats. In pre-treatment, rats were co-administered 200 mg/kg of fruit extract with DEN for 14 weeks. In post-treatment, the extract was co-administered after 8-weeks of DEN-induction for 14 weeks. Liver function test, haematological test, oxidative stress markers, relative liver weight, number of cancer nodules and histopathological parameters were determined.Results: Annona muricata fruit extract =significantly lowered cell proliferation counts. The chloroform-fraction possessed higher activity (IC50=(53.7±4.3) μg/mL)The chloroform fraction inhibited cell migration, which was significant compared to curcumin. Further investigations regarding the mode of anticancer activity revealed that the chloroform fraction induced apoptosis. The cell cycle analysis indicated that cells were being arrested at G0/G1. In the in vivo studies, the DEN-control group showed a significant decrease in body weights with increased mortality rate, hepatic nodules, and impairment of liver function compared to normal rats. The rats pre-treated and post-treated with the extract showed positive results with significant improvement in the parameters that were adversely affected by DEN. In addition, other adverse effects of DEN, such as blood dyscrasias and hepatic endogenous antioxidant, were significantly attenuated by Annona muricata fruit extract.Conclusions: The Annona muricata fruit extract has anticancer activity when tested by in vitro and in vivo hepatocellular cancer models.展开更多
A treatment based on the acetogenin fraction of the methanol extract of Rollinia occidentalis seeds was applied to soybean crops for three consecutive years. In relation to the control population, the treatment reduce...A treatment based on the acetogenin fraction of the methanol extract of Rollinia occidentalis seeds was applied to soybean crops for three consecutive years. In relation to the control population, the treatment reduced the population of Anticarsia gemmatalis, Rachiplusia nu, Pseudoplusia includens, Loxostege bifidalis and Spodoptera frugiperda to 52% and 65% after 48 h of application at concentrations of 500 and 750 μg/mL respectively, while low toxic effects were detected on natural enemies. The extract treatment at 500 μg/mL and a solution of the annonaceous acetogenin, squamocin, at 50 and 100 μg/mL, were also applied to a corn field to produce 75%, 93% and 100% mortality rates on the population of S. frugiperda, respectively, after 72 h of application. In addition, damages caused by lepidopterans in treated crops were lower than those observed in non treated fields, evaluated by residual biomass. This statement is based on data from trials with the commercially available insecticides lufenuron and cypermethrin.展开更多
Muricatenol 1, a new acetogenin, has been isolated from the seeds of Annona muricata L.. Compound 1 is a C-37 acetogenin without any THF rings. with four hydroxyls and one double bond in the long aliphatic chain. The ...Muricatenol 1, a new acetogenin, has been isolated from the seeds of Annona muricata L.. Compound 1 is a C-37 acetogenin without any THF rings. with four hydroxyls and one double bond in the long aliphatic chain. The hydroxyls of 1 are located at C-4, C-10, C-18 and C-19. respectively. The vicinal diet at C-18/C-19 is threo-configuration, and the double bond at C-14/C-15 is cis-configuration.展开更多
The Aedes(Ae.)aegypti and Ae.albopictus mosquitoes are vectors of epidemiologically relevant arboviruses in the public health context,such as the dengue,Zika and chikungunya viruses.Among the alternatives to synthetic...The Aedes(Ae.)aegypti and Ae.albopictus mosquitoes are vectors of epidemiologically relevant arboviruses in the public health context,such as the dengue,Zika and chikungunya viruses.Among the alternatives to synthetic insecticides for the control of these vectors,the use of natural plant products deserves attention.This review summarizes findings on the larvicidal potential of plant extracts on Ae.aegypti and Ae.albopictus,as well as the potential of isolated compounds from plants of the Annonaceae and Piperaceae families against these vectors.Descriptors related to larvicidal activity of plant extracts and isolated compounds in Aedes spp.in the Web of Science database were used,for plant extracts considering publications between 2000 and 2019.A total of 859 articles were analyzed for plant extracts and estimates of lethal concentration values(LC50 and LC90).In the end,95 articles that presented the larvicidal potential of 150 plant species from 52 families were analyzed.The two families most studied for this activity were Fabaceae and Asterace Aedes.The plant families with the best LC50 values against mosquitoes were Piperaceae and Annonaceae.Larvicidal activity of 50 acetogenins has already been identified on Ae.aegypti,and 29 of them presented LC50 below 10μg/mL,as well as the larvicidal activity of 8 compounds isolated from Piperaceae.Therefore,plants of these two families are promising for the development of commercial botanical larvicides in the form of extracts and isolated substances,as well as the production via organic synthesis of the most active compounds.展开更多
Calamistrin E, the first Annonaceous acetogenin with C=C bond in the aliphatic chain from the genus Uvaria was isolated from U. calamistrata. Its structure including relative and absolute configurations was determined...Calamistrin E, the first Annonaceous acetogenin with C=C bond in the aliphatic chain from the genus Uvaria was isolated from U. calamistrata. Its structure including relative and absolute configurations was determined by chemical derivation and spectral analysis.展开更多
AA005(1),a potent anticancer mimicking molecule of natural Annonaceous acetogenin,features a central C_(2)-symmetric triglycol moiety and three stereogenic centers.To support ongoing animal studies,a scalable 10-step ...AA005(1),a potent anticancer mimicking molecule of natural Annonaceous acetogenin,features a central C_(2)-symmetric triglycol moiety and three stereogenic centers.To support ongoing animal studies,a scalable 10-step synthesis of AA005(1) has been studied,optimized and accomplished in this work,starting from commercially available economic materials ethylene glycol and(R)-epichlorohydrin.A regio-and stereo-controlled BF_(3)·Et_(2)O-promoted epoxide opening of(R)-epichlorohydrin with ethylene glycol was investigated,optimized and successfully applied to the scalable preparation of the crucial fragment 6 a with C_(2)-symmetry.Further successive epoxide openings elaborated both two side chains and the whole skeleton with proper nucleophiles and electrophiles.Comparison and optimization of the reaction sequences finally led to completion of a new multi-gram synthesis ofAA005(1) with satisfactory enantiomeric and diastereomeric purity.展开更多
We examined the chemical constitution of the red alga Laurencia saitoi Perestenko,collected from Katsuura,Boso Peninsula,Chiba Prefecture,Japan.This specimen produced a new polyhalogenated acetogenin,named katsuural-l...We examined the chemical constitution of the red alga Laurencia saitoi Perestenko,collected from Katsuura,Boso Peninsula,Chiba Prefecture,Japan.This specimen produced a new polyhalogenated acetogenin,named katsuural-lene(1),which structure was determined by the spectral methods,along with known diterpene,deoxyparguerol(2)and triterpene,thyrsiferol(3).In this paper we describe the structural elucidation of katsuurallene together with some biological activities.展开更多
The two new diarylheptanoids, 1,7-bis(4-hydroxyphenyl)-1,4,6 (l) and aecrogenin G (2) were Synthesized starting from 4-hydroxybenzaldehyde (3) and acetone
Atemoyacin A, a new annonaceous acetogenin was isolated from the alcoholic extract of the seeds of Annona atemoya Hort (Annonaceae). Its structure and relative configuration were elucidated on the basis of the spectra...Atemoyacin A, a new annonaceous acetogenin was isolated from the alcoholic extract of the seeds of Annona atemoya Hort (Annonaceae). Its structure and relative configuration were elucidated on the basis of the spectral analysis.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81573577,81274057 and 81403082)
文摘Eight new annonaceous acetogenins, squamotin A–D(1–4), annosquatin IV–V(5 and 6), muricin O(7) and squamosten B(8), together with four known ones(9–12) were isolated from the seeds of Annona squamosa. Their structures were elucidated by chemical methods and spectral data. The inhibitory activities of compound 1–9 against three multidrug resistance cell lines were evaluated. All tested compounds showed strong cytotoxicity.
文摘Toxic and nutritional effects of annonaceous acetogenins and their semisynthetic analogues on Spodoptera frugiperda were evaluated. Structural modification of the natural ACG, blocking the OH flanking THF with MOM, allowed us to suggest the mode of action of ACG in the membrane. Our study emphasizes the role of the flanking OH and acetyl groups of THF with the membrane hydrophilic polar head groups. They are essential structural factors in the ACG that facilitate the intermolecular interaction that dehydrates the membrane and makes it potentially toxic against Spodoptera frugiperda.
文摘Background: Annonaceous acetogenins enclose a large number of biological activities, among which the insecticidal stands out. Methods: We report herein the biocide effects of natural acetogenins from Annona squamosa, A.?muricata and A. montana seeds: annonacin, cis-annonacin, cis-annonacin-10- one, asimicin, rolliniastatin-2, cherimolin-1, cherimolin-2, almuñequin, and two β-OH acetogenins: laherradurin and itrabin on Spodoptera frugiperda Smith (Lepidoptera: Noctuidae). Also, some acetylated and methoxy methylated ACG derivatives were synthesized and evaluated: annonacin (3 OAc), annonacin (4 OAc), asimicin (3 OAc), rolliniastatin-2 (3 OAc), rolliniastatin-2 (MOM), laherradurin (3 OAc) and itrabin (3 OAc). Results: The natural acetogenin rolliniastatin-2 (100 μg·g-1 of diet) produced the most important toxic action causing 100% mortality of early instar larvae. Derivatization of ACG yielded compounds that produced nutritional alterations. The incorporation of rolliniastatin-2 (3 OAc) and rolliniastatin-2 (3 MOM) (100 μg·g-1) into the artificial diet of Spodoptera frugiperdadisplayed the strongest antifeedant effects causing marked decreasings in larval growth and adult lethal malformations. Conclusion: Natural acetogenins are promising metabolites for insect control. Derivatization of these compounds reduces their toxicity to early instar larvae.
文摘Annonaceous acetogenins enclose a large number of biological activities, among which the insecticidal stands out. <em>Spodoptera frugiperda</em> is a pest that affects corn crops among others and has a great capacity to develop resistance to traditional insecticides, which represents sufficient reasons for the search for new alternatives for their control. The objective of this study was to determine the appropriate concentration and screening new natural insecticides against second instar larvae of <em>S. frugiperda</em>, under glasshouse conditions on <em>Zea mays</em> L. Natural products such as annonaceous acetogenins and some acetylated and methoxy methylated ACG derivatives and the commercial product Lambda-cyhalotrin (LC) were evaluated. The percent mortalities of <em>S. frugiperda </em>larvae in glasshouse conditions were recorded after 24, 48 and 72 h of treatment application. The results showed that the acetogenins tested were significantly (P < 0.05) different in relation to pest mortality than untreated check. After 72 h of treatment application the highest percent mortalities were obtained with the mixture of two natural products, rolliniastatin-2 (<strong>5</strong>) (100 μg/mL) + squamocin (<strong>6</strong>) (100 μg/mL) + LC (50 μg/mL) that proved the most effective and gave (100%), while rolliniastatin-2 (<strong>5</strong>) at 100 μg/mL alone, gave lowest percent mortality (65%), followed by squamocin (<strong>6</strong>) at 100 μg/mL (55%) and LC at 50 μg/mL (30%). The acetylated and methoxy methylated ACGs derivatives caused very low mortality (25% - 35%). It is recommended the mixture as a management option of <em>S. frugiperda</em> as a component of integrated pest management. The results allow us to infer that the addition of natural ACGs synergizes the insecticidal activity of the commercial product. Finding a new ecological alternative for insect control.
文摘Annonaceous acetogenins (ACG), belonging to the family Annonaceae, represent a class of bioactive compounds whose toxic effects have been reported for several spe-cies of insects. Given their insecticidal properties, we first carried out the isolation of the ACG from a Brazilian collection of the seeds of Annona squamosa (Annonaceae) and prepared their methoxy methylated (MOM) and acetylated (OAc) derivatives by chemical methods. ACG analogues were semi-synthesized and characterized by spec-troscopic techniques (<sup>1</sup>H and <sup>13</sup>C-NMR). We isolated ten natural acetogenins: squamo-cin, molvizarin, motrilin, rolliniastatin-2, almunequin, cherimolin-1, cherimolin-2, an-nonacin, squamocin D and asiminecin. The main objective of this study is to report the antifeedant, toxic and nutritional effects of three of those natural acetogenins and their acetylated and methoxy methylated derivatives on Spodoptera frugiperda Smith (Lep-idoptera: Noctuidae). The natural ACGs squamocin and molvizarin killed 100% of S. frugiperda larvae, followed by motrilin (80%). Acetylated derivatives had less toxic and nutritional effects that led to pupal mortality and adult fatal malformations. The addition of MOM derivatives to the larval diet has not toxic effects on larvae, but significantly reduces growth rate and efficiency in conversion of ingested food into biomass, affecting adult survival.
文摘Two mild-cytotoxic bistetrahydrofuran (THF) ring annonaceous acetogenins named calamistrins F(1) and G(2) were isolated from the ethanolic extract of the roots of U. calamistrata Hance. Their structures including the relative and absolute configurations were determined by chemical derivation and spectral analysis. Calamistrins F and G were a pair of epimers at C-26 which both had THF ring from C-18 to C-25 and three OH groups at C-5, C-17 and C-26.
基金Supported by National Mega-project for Innovative Drugs(No.2012ZX09301002-001-026 and 2009ZX09103-390)Beijing Natural Science Foundation(No.7122112)
文摘Objective： To confirm the anticancer effect of total annonaceous acetogenins （TAAs） abstracted from Annona squamosa Linn. on human hepatocarcinoma. Methods： The inhibitory effect of TAAs was demonstrated in H,,-bearing mice. The potency of TAAs was confirmed as its 50% inhibiting concentration （IC50） on Bel-7402 cell under Sulfur Rhodamine B staining. Both underlying mechanisms were explored as cellular apoptosis and cell cycle under flow cytometry. Mitochondrial and recipient apoptotic pathways were differentiated as mitochondrial membrane potential under flow cytometry and caspases activities under fluorescence analysis. Results： The inhibitory rate of TAAs in mice was 50.98% at 4 mg/kg dose. The IC50 of TAAs on Bel-7402 was 20.06 μg/mL （15.13-26.61 μg/mL）. Effective mechanisms of TAAs were confirmed as both of arresting cell cycle at G1 phase and inducing apoptosis dose- and time-dependently. Mitochondrial and recipient pathways involved in apoptotic actions of TAAs. Conclusion： TAAs is effective for hepatocarcinoma, via inhibiting proliferation and inducing apoptosis.
文摘A new Annonaceous acetogenin, squamostolide (1), was isolated from the seeds of Annona squamosa. Its structure was elucidated based on spectroscopic methods and comparison with known compounds. It is the first example of Annonaceous acetogenin with each of the two ends of the aliphatic chain bearing a g-lactone. The new compound exhibited cytotoxic activity in vitro against bel-7402 and CNE2 human tumor cell lines.
文摘Annona muricata(A.muricata)is a tropical plant species belonging to family Annonaceae and known for its many medicinal uses.This review focuses on the research history of its traditional uses,phytochemicals,pharmacological activities,toxicological aspects of the extracts and isolated compounds,as well as the in vitro propagation studies with the objective of stimulating further studies on this plant for human consumption and treatment.A.muricata extracts have been identified in tropical regions to traditionally treat diverse conditions ranging from fever to diabetes and cancer.More than 200 chemical compounds have been identified and isolated from this plant,the most important being alkaloids,phenols and acetogenins.Using in vitro studies,its extracts and phytochemicals have been characterized as antioxidant,anti-microbial,anti-inflammatory,insecticidal,larvicidal,and cytotoxic to cancer cells.In vivo studies have revealed anxiolytic,antistress,anti-inflammatory,immunomodulatory,antimalarial,antidepressant,gastro protective,wound healing,hepato-protective,hypoglycemic,anticancer and anti-tumoral activities.In silico studies have also been reported.In addition,clinical studies support the hypoglycemic as well as some anticancer activities.Mechanisms of action of some pharmacological activities have been elucidated.However,some phytochemical compounds isolated from A.muricata have shown a neurotoxic effect in vitro and in vivo,and therefore,these crude extracts and isolated compounds need to be further investigated to define the magnitude of the effects,optimal dosage,and mechanisms of action,long-term safety,and potential side effects.Additionally,more clinical studies are necessary to support the therapeutic potential of this plant.Some studies were also found to have successfully regenerated the plant in vitro,but with limited success.The reported toxicity notwithstanding,A.muricata extracts seem to be some of the safest and promising therapeutic agents of the 21st century and beyond that need to be studied further for better medicinal formulations and diseases management.
文摘Objective: To evaluate the anticancer potentials of Annona muricata fruit by in vitro and in vivo methods. Methods: The ethanolic extract of Annona muricata fruit was prepared by Soxhlet extraction method and further fractionated with petroleum ether, ethyl acetate and chloroform. The fractions were tested for cytotoxicity, apoptosis, scratch wound assay, and cell cycle analysis. IC50, apoptotic index and percentage cell migration were determined using HepG2 cells. For the in vivo studies, hepatocellular carcinoma was induced by administering 0.01% diethylnitrosamine(DEN) in drinking water in Wistar rats. In pre-treatment, rats were co-administered 200 mg/kg of fruit extract with DEN for 14 weeks. In post-treatment, the extract was co-administered after 8-weeks of DEN-induction for 14 weeks. Liver function test, haematological test, oxidative stress markers, relative liver weight, number of cancer nodules and histopathological parameters were determined.Results: Annona muricata fruit extract =significantly lowered cell proliferation counts. The chloroform-fraction possessed higher activity (IC50=(53.7±4.3) μg/mL)The chloroform fraction inhibited cell migration, which was significant compared to curcumin. Further investigations regarding the mode of anticancer activity revealed that the chloroform fraction induced apoptosis. The cell cycle analysis indicated that cells were being arrested at G0/G1. In the in vivo studies, the DEN-control group showed a significant decrease in body weights with increased mortality rate, hepatic nodules, and impairment of liver function compared to normal rats. The rats pre-treated and post-treated with the extract showed positive results with significant improvement in the parameters that were adversely affected by DEN. In addition, other adverse effects of DEN, such as blood dyscrasias and hepatic endogenous antioxidant, were significantly attenuated by Annona muricata fruit extract.Conclusions: The Annona muricata fruit extract has anticancer activity when tested by in vitro and in vivo hepatocellular cancer models.
文摘A treatment based on the acetogenin fraction of the methanol extract of Rollinia occidentalis seeds was applied to soybean crops for three consecutive years. In relation to the control population, the treatment reduced the population of Anticarsia gemmatalis, Rachiplusia nu, Pseudoplusia includens, Loxostege bifidalis and Spodoptera frugiperda to 52% and 65% after 48 h of application at concentrations of 500 and 750 μg/mL respectively, while low toxic effects were detected on natural enemies. The extract treatment at 500 μg/mL and a solution of the annonaceous acetogenin, squamocin, at 50 and 100 μg/mL, were also applied to a corn field to produce 75%, 93% and 100% mortality rates on the population of S. frugiperda, respectively, after 72 h of application. In addition, damages caused by lepidopterans in treated crops were lower than those observed in non treated fields, evaluated by residual biomass. This statement is based on data from trials with the commercially available insecticides lufenuron and cypermethrin.
文摘Muricatenol 1, a new acetogenin, has been isolated from the seeds of Annona muricata L.. Compound 1 is a C-37 acetogenin without any THF rings. with four hydroxyls and one double bond in the long aliphatic chain. The hydroxyls of 1 are located at C-4, C-10, C-18 and C-19. respectively. The vicinal diet at C-18/C-19 is threo-configuration, and the double bond at C-14/C-15 is cis-configuration.
文摘The Aedes(Ae.)aegypti and Ae.albopictus mosquitoes are vectors of epidemiologically relevant arboviruses in the public health context,such as the dengue,Zika and chikungunya viruses.Among the alternatives to synthetic insecticides for the control of these vectors,the use of natural plant products deserves attention.This review summarizes findings on the larvicidal potential of plant extracts on Ae.aegypti and Ae.albopictus,as well as the potential of isolated compounds from plants of the Annonaceae and Piperaceae families against these vectors.Descriptors related to larvicidal activity of plant extracts and isolated compounds in Aedes spp.in the Web of Science database were used,for plant extracts considering publications between 2000 and 2019.A total of 859 articles were analyzed for plant extracts and estimates of lethal concentration values(LC50 and LC90).In the end,95 articles that presented the larvicidal potential of 150 plant species from 52 families were analyzed.The two families most studied for this activity were Fabaceae and Asterace Aedes.The plant families with the best LC50 values against mosquitoes were Piperaceae and Annonaceae.Larvicidal activity of 50 acetogenins has already been identified on Ae.aegypti,and 29 of them presented LC50 below 10μg/mL,as well as the larvicidal activity of 8 compounds isolated from Piperaceae.Therefore,plants of these two families are promising for the development of commercial botanical larvicides in the form of extracts and isolated substances,as well as the production via organic synthesis of the most active compounds.
文摘Calamistrin E, the first Annonaceous acetogenin with C=C bond in the aliphatic chain from the genus Uvaria was isolated from U. calamistrata. Its structure including relative and absolute configurations was determined by chemical derivation and spectral analysis.
基金Financial support from the National Natural Science Foundation of China(Nos.21532002,21761142001 and 21778031)National Key Research and Development Program(No.2018YFC0310900)is greatly appreciated。
文摘AA005(1),a potent anticancer mimicking molecule of natural Annonaceous acetogenin,features a central C_(2)-symmetric triglycol moiety and three stereogenic centers.To support ongoing animal studies,a scalable 10-step synthesis of AA005(1) has been studied,optimized and accomplished in this work,starting from commercially available economic materials ethylene glycol and(R)-epichlorohydrin.A regio-and stereo-controlled BF_(3)·Et_(2)O-promoted epoxide opening of(R)-epichlorohydrin with ethylene glycol was investigated,optimized and successfully applied to the scalable preparation of the crucial fragment 6 a with C_(2)-symmetry.Further successive epoxide openings elaborated both two side chains and the whole skeleton with proper nucleophiles and electrophiles.Comparison and optimization of the reaction sequences finally led to completion of a new multi-gram synthesis ofAA005(1) with satisfactory enantiomeric and diastereomeric purity.
基金supported by JSPS KAKENHI Grant Numbers 18K05799 and 21K14904.
文摘We examined the chemical constitution of the red alga Laurencia saitoi Perestenko,collected from Katsuura,Boso Peninsula,Chiba Prefecture,Japan.This specimen produced a new polyhalogenated acetogenin,named katsuural-lene(1),which structure was determined by the spectral methods,along with known diterpene,deoxyparguerol(2)and triterpene,thyrsiferol(3).In this paper we describe the structural elucidation of katsuurallene together with some biological activities.
文摘The two new diarylheptanoids, 1,7-bis(4-hydroxyphenyl)-1,4,6 (l) and aecrogenin G (2) were Synthesized starting from 4-hydroxybenzaldehyde (3) and acetone
文摘Atemoyacin A, a new annonaceous acetogenin was isolated from the alcoholic extract of the seeds of Annona atemoya Hort (Annonaceae). Its structure and relative configuration were elucidated on the basis of the spectral analysis.
