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新型苯基(2H-四唑-5-基)甲胺衍生物的设计、合成及抗真菌活性评估

Design, synthesis, and evaluations of antifungal activity of novel phenyl(2H-tetrazol-5-yl)methanamine derivatives.

作者信息

Salake Amol B, Chothe Aparna S, Nilewar Shrikant S, Khilare Madhavi, Meshram Rutuja S, Pandey Abhishek A, Kathiravan M K

机构信息

Department of Pharmaceutical Chemistry (PG), AISSMS College of Pharmacy, Kennedy road, Near RTO, Pune, 411001 Maharashtra India.

Department of Pharmaceutical Chemistry (PG), Sinhgad College of Pharmacy, Off. Sinhgad road, Vadgaon (Bk.), Pune, 411041 Maharashtra India.

出版信息

J Chem Biol. 2013 Sep 12;7(1):29-35. doi: 10.1007/s12154-013-0103-8.

Abstract

Fungal infections pose a continuous and serious threat to human health and life. The intrinsic resistance has been observed in many genera of fungi. Many fungal infections are caused by opportunistic pathogens that may be endogenous (Candida infections) or acquired from the environment (Cryptococcus and Aspergillus infections). So, new therapeutic strategies are needed to combat various fungal infections. Fluconazole shows good antifungal activity with relatively low toxicity and is preferred as first line antifungal therapy, but it has suffered from severe drug resistance. So, there is a need to design novel analogues by modification of fluconazole-like structure. A novel series of phenyl(2H-tetrazol-5-yl)methanamine derivatives were synthesized by reaction of α-amino nitrile with sodium azide and ZnCl2 in presence of isopropyl alcohol. They were evaluated for antifungal activity against Candida albicans and Aspergillus niger and subjected to docking study against 1EA1.

摘要

真菌感染对人类健康和生命构成持续且严重的威胁。在许多真菌属中都观察到了固有抗性。许多真菌感染是由机会性病原体引起的,这些病原体可能是内源性的(念珠菌感染)或从环境中获得的(隐球菌和曲霉感染)。因此,需要新的治疗策略来对抗各种真菌感染。氟康唑显示出良好的抗真菌活性且毒性相对较低,是首选的一线抗真菌治疗药物,但它已出现严重的耐药性。所以,有必要通过修饰氟康唑样结构来设计新型类似物。通过α-氨基腈与叠氮化钠和氯化锌在异丙醇存在下反应,合成了一系列新型的苯基(2H-四唑-5-基)甲胺衍生物。对它们针对白色念珠菌和黑曲霉的抗真菌活性进行了评估,并对其进行了针对1EA1的对接研究。

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