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苦藏冬叶中的托品酮生物碱作为新型有效的抗利什曼原虫化合物;分离、结构鉴定、抗利什曼原虫活性和分子对接研究。

Tropolone alkaloids from Colchicum kurdicum (Bornm.) Stef. (Colchicaceae) as the potent novel antileishmanial compounds; purification, structure elucidation, antileishmanial activities and molecular docking studies.

机构信息

Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

Exp Parasitol. 2020 Jun;213:107902. doi: 10.1016/j.exppara.2020.107902. Epub 2020 Apr 27.

Abstract

Natural compounds played an important role for prevention and treatment of the disease as well as are the important compounds for the design of the new bioactive compounds. In this study, eight tropolone alkaloids were isolated from Colchicum kurdicum including colchicoside, 2-demethyl colchicine, 3-demethyl colchicine, demecolcine, colchifoline, N-deacetyl-N-formyl colchicine, colchicine and cornigerine by column and preparative thin layer chromatography. The chemical structures were identified by H NMR and C NMR spectroscopy. Moreover, the antileishmanial activity on Leishmania major, anti-inflammatory activity, iron chelating activity and toxicity studies including hemolytic activity, brine shrimp toxicity, cytotoxicity and acute toxicity and docking study of all isolated bioactive compounds were evaluated. As result, colchicoside and colchicine had potent leishmanicidal effects and N-deacetyl-N-formyl colchicine and cornigerine had the highest anti-inflammatory effects. All compounds had the significant iron chelating activity. According to toxicity studies, isolated compounds showed the low hemolytic activity and cytotoxicity, high LC, LC and LD. In the molecular docking study, colchicoside had the high dockscore. According to the study, with future studies all isolated compounds could be used for design the novel antileishmanial drugs.

摘要

天然化合物在疾病的预防和治疗中起着重要作用,也是设计新的生物活性化合物的重要化合物。在这项研究中,从苦苣菜中分离出了 8 种托罗酮生物碱,包括秋水仙素、2-去甲基秋水仙碱、3-去甲基秋水仙碱、去甲酰基-去甲秋水仙碱、秋水仙碱、N-脱乙酰-N-甲酰基秋水仙碱、秋水仙碱和玉米素。通过柱层析和制备薄层层析对其进行了分离。通过 1H NMR 和 13C NMR 光谱对其化学结构进行了鉴定。此外,还对所有分离得到的生物活性化合物进行了抗利什曼原虫活性、抗炎活性、铁螯合活性、溶血活性、卤虫毒性、细胞毒性和急性毒性以及对接研究。结果表明,秋水仙素和秋水仙碱具有较强的杀利什曼原虫活性,N-脱乙酰-N-甲酰基秋水仙碱和玉米素具有最强的抗炎活性。所有化合物均具有显著的铁螯合活性。根据毒性研究,分离得到的化合物表现出低溶血活性和细胞毒性、高 LC、LC 和 LD。在分子对接研究中,秋水仙素具有较高的对接评分。根据研究结果,随着未来的研究,所有分离得到的化合物都可用于设计新型抗利什曼原虫药物。

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