The anticancer potential of quassinoids has attracted a great deal of attention for decades,and scientific data revealing their possible applications in cancer management are continuously increasing in the literature....The anticancer potential of quassinoids has attracted a great deal of attention for decades,and scientific data revealing their possible applications in cancer management are continuously increasing in the literature.Aside from the potent cytotoxic and antitumor properties of these degraded triterpenes,several quassinoids have exhibited synergistic effects with anticancer drugs.This article provides an overview of the potential anticancer properties of quassinoids,including their cytotoxic and antitumor activities,mechanisms of action,safety evaluation,and potential benefits in combination with anticancer drugs.展开更多
Main observation and conclusion Quassinoids,a class of highly oxygenated triterpenes,have been isolated as bitter principles from the plants of Simaroubaceae family.Five new quassinoids,chouchunlactone A-E(1-5),and tw...Main observation and conclusion Quassinoids,a class of highly oxygenated triterpenes,have been isolated as bitter principles from the plants of Simaroubaceae family.Five new quassinoids,chouchunlactone A-E(1-5),and two known ones were identified from the root barks of Ailanthus altissima Swingle(Simaroubaceae).The chemical structures of the new compounds were deduced by spectroscopic data analyses,NMR calculations and DP4+probability analysis.The absolute configurations were defined by comparison of their experimental and calculated electronic circular dichroism(ECD)spectra data,and compounds 1-2 were further confirmed by single-crystal X-ray diffraction.Biologically,compound 5 showed potencies equivalent to sorafenib(IC50 value,9.70μmol·L–1)against HepG2 cells.The Hoechst 33342 staining,JC-1 fluorescent dye and Annexin V/PI analysis studies demonstrated that 5 can induce apoptosis and attenuate mitochondrial membrane potential(MMP)in HepG2 cells.展开更多
Eurycoma longifolia Jack(E.longifolia) is a well-recognized traditional herbal medicine that offers a wide dynamic range of biomedical applications including anti-osteoporotic, anticancer, anti-proliferative, anti-mal...Eurycoma longifolia Jack(E.longifolia) is a well-recognized traditional herbal medicine that offers a wide dynamic range of biomedical applications including anti-osteoporotic, anticancer, anti-proliferative, anti-malarial, antimicrobial, antioxidant, aphrodisiac, antiinflammatory, anxiolytic, anti-diabetic, anti-rheumatism and anti-ulcer properties.This review aims to overview the pharmacokinetic and a pharmacodynamic algorithm of E.longifolia and its bioactive components.Analysis of pharmacokinetic profile revealed that E.longifolia exhibit higher bioavailability, high volume of distribution, slow elimination rate, and does not show inhibitory effects on cytochrome P450 isoenzymes.E.longifolia has been used, alone or in combination with other pharmacological agents, in the form of crude extracts, standard extracts, or decoctions of different plant parts(i.e., herbs, shrubs, stem, leaves, and roots) for the treatment of various ailments in animals and humans.Among various bioactive constituents, eurycomanone has been found to be the most remarkable, super-stable, versatile, and most potent phytochemical(isolated or extracted from root extracts) against various types of animals and human diseases.Based on its well-established pharmacokinetic and pharmacodynamic profiles, we suggested that E.longifolia can be a well-accepted complementary and alternative medicine for the treatment of different types of human ailments.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
基金supported by the National Natural Science Foundation of China(82274085)the Natural Science Foundation of Jiangsu Province(BK20220478)the Natural Science Foundation of Jiangsu Higher Education institutions of China(22KJB360010).
文摘The anticancer potential of quassinoids has attracted a great deal of attention for decades,and scientific data revealing their possible applications in cancer management are continuously increasing in the literature.Aside from the potent cytotoxic and antitumor properties of these degraded triterpenes,several quassinoids have exhibited synergistic effects with anticancer drugs.This article provides an overview of the potential anticancer properties of quassinoids,including their cytotoxic and antitumor activities,mechanisms of action,safety evaluation,and potential benefits in combination with anticancer drugs.
基金This work was financially supported by the National Natural Science Foundation of China(No.81872767)the Career Development Support Plan for the Young and Middle-aged Teachers in Shenyang Pharmaceutical University(No.ZQN2018006)+1 种基金the Pro ject funded by China Postdoctoral Science Foundation(No.2020M680987)the Project of Innovation Team(No.LT2015027)of Liaoning in China.
文摘Main observation and conclusion Quassinoids,a class of highly oxygenated triterpenes,have been isolated as bitter principles from the plants of Simaroubaceae family.Five new quassinoids,chouchunlactone A-E(1-5),and two known ones were identified from the root barks of Ailanthus altissima Swingle(Simaroubaceae).The chemical structures of the new compounds were deduced by spectroscopic data analyses,NMR calculations and DP4+probability analysis.The absolute configurations were defined by comparison of their experimental and calculated electronic circular dichroism(ECD)spectra data,and compounds 1-2 were further confirmed by single-crystal X-ray diffraction.Biologically,compound 5 showed potencies equivalent to sorafenib(IC50 value,9.70μmol·L–1)against HepG2 cells.The Hoechst 33342 staining,JC-1 fluorescent dye and Annexin V/PI analysis studies demonstrated that 5 can induce apoptosis and attenuate mitochondrial membrane potential(MMP)in HepG2 cells.
基金Ministry of Agriculture for providing New Application for Herbal Research Grant Scheme(NRGS)(NH1014D040) and supports
文摘Eurycoma longifolia Jack(E.longifolia) is a well-recognized traditional herbal medicine that offers a wide dynamic range of biomedical applications including anti-osteoporotic, anticancer, anti-proliferative, anti-malarial, antimicrobial, antioxidant, aphrodisiac, antiinflammatory, anxiolytic, anti-diabetic, anti-rheumatism and anti-ulcer properties.This review aims to overview the pharmacokinetic and a pharmacodynamic algorithm of E.longifolia and its bioactive components.Analysis of pharmacokinetic profile revealed that E.longifolia exhibit higher bioavailability, high volume of distribution, slow elimination rate, and does not show inhibitory effects on cytochrome P450 isoenzymes.E.longifolia has been used, alone or in combination with other pharmacological agents, in the form of crude extracts, standard extracts, or decoctions of different plant parts(i.e., herbs, shrubs, stem, leaves, and roots) for the treatment of various ailments in animals and humans.Among various bioactive constituents, eurycomanone has been found to be the most remarkable, super-stable, versatile, and most potent phytochemical(isolated or extracted from root extracts) against various types of animals and human diseases.Based on its well-established pharmacokinetic and pharmacodynamic profiles, we suggested that E.longifolia can be a well-accepted complementary and alternative medicine for the treatment of different types of human ailments.
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.
