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诃子(使君子科)茎皮中的化合物对一些致病性酵母和具有代谢意义的酶具有强效抑制作用。

Compounds from Terminalia mantaly L. (Combretaceae) Stem Bark Exhibit Potent Inhibition against Some Pathogenic Yeasts and Enzymes of Metabolic Significance.

作者信息

Tchuente Tchuenmogne Marthe Aimée, Kammalac Thierry Ngouana, Gohlke Sebastian, Kouipou Rufin Marie Toghueo, Aslan Abdulselam, Kuzu Muslum, Comakli Veysel, Demirdag Ramazan, Ngouela Silvère Augustin, Tsamo Etienne, Sewald Norbert, Lenta Bruno Ndjakou, Boyom Fabrice Fekam

机构信息

Laboratory of Natural Products and Organic Synthesis, Department of Organic Chemistry, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon.

Antimicrobial & Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Department of Biochemistry, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon.

出版信息

Medicines (Basel). 2017 Jan 24;4(1):6. doi: 10.3390/medicines4010006.

Abstract

: Pathogenic yeasts resistance to current drugs emphasizes the need for new, safe, and cost-effective drugs. Also, new inhibitors are needed to control the effects of enzymes that are implicated in metabolic dysfunctions such as cancer, obesity, and epilepsy. The anti-yeast extract from (Combretaceae) was fractionated and the structures of the isolated compounds established by means of spectroscopic analysis and comparison with literature data. Activity was assessed against , and using the microdilution method, and against four enzymes of metabolic significance: glucose-6-phosphate dehydrogenase, human erythrocyte carbonic anhydrase I and II, and glutathione -transferase. Seven compounds, 3,3'-di--methylellagic acid 4'--α-rhamnopyranoside; 3--methylellagic acid; arjungenin or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid; arjunglucoside or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid glucopyranoside; 2α,3α,24-trihydroxyolean-11,13(18)-dien-28-oïc acid; stigmasterol; and stigmasterol 3--β-d-glucopyranoside were isolated from the extract. Among those, 3,3'-di--methylellagic acid 4'--α-rhamnopyranoside, 3--methylellagic acid, and arjunglucoside showed anti-yeast activity comparable to that of reference fluconazole with minimal inhibitory concentrations (MIC) below 32 µg/mL. Besides, Arjunglucoside potently inhibited the tested enzymes with 50% inhibitory concentrations (IC) below 4 µM and inhibitory constant (Ki) <3 µM. The results achieved indicate that further SAR studies will likely identify potent hit derivatives that should subsequently enter the drug development pipeline.

摘要

致病性酵母对现有药物的耐药性凸显了开发新型、安全且具有成本效益药物的必要性。此外,还需要新型抑制剂来控制与癌症、肥胖症和癫痫等代谢功能障碍相关的酶的作用。对风车子属(使君子科)的抗酵母提取物进行了分级分离,并通过光谱分析以及与文献数据对比确定了分离出的化合物的结构。采用微量稀释法评估了提取物对白色念珠菌、热带念珠菌和光滑念珠菌的活性,并评估了其对四种具有代谢意义的酶的活性:葡萄糖-6-磷酸脱氢酶、人红细胞碳酸酐酶I和II以及谷胱甘肽-S-转移酶。从提取物中分离出了七种化合物:3,3'-二-O-甲基鞣花酸4'-O-α-鼠李吡喃糖苷;3-O-甲基鞣花酸;阿琼皂苷元或2,3,19,23-四羟基齐墩果-12-烯-28-酸;阿琼糖苷或2,3,19,23-四羟基齐墩果-12-烯-28-酸葡萄糖吡喃糖苷;2α,3α,24-三羟基齐墩果-11,13(18)-二烯-28-酸;豆甾醇;以及豆甾醇3-O-β-D-葡萄糖吡喃糖苷。其中,3,3'-二-O-甲基鞣花酸4'-O-α-鼠李吡喃糖苷、3-O-甲基鞣花酸和阿琼糖苷显示出与参比氟康唑相当的抗酵母活性,最低抑菌浓度(MIC)低于32μg/mL。此外,阿琼糖苷对所测试的酶具有强效抑制作用,50%抑制浓度(IC)低于4μM,抑制常数(Ki)<3μM。所取得的结果表明,进一步的构效关系研究可能会鉴定出有潜力的先导衍生物,随后这些衍生物应进入药物研发流程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a718/5597071/e57a3e39bd7c/medicines-04-00006-g001.jpg

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