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新型海洋溴代吡咯生物碱 1,3,4-噁二唑衍生物的合成与评价及其作为抗菌剂的研究。

Synthesis and evaluation of novel 1,3,4-oxadiazole derivatives of marine bromopyrrole alkaloids as antimicrobial agent.

机构信息

SPP School of Pharmacy and Technology Management, NMIMS University, Vile Parle, Mumbai, India.

出版信息

Bioorg Med Chem Lett. 2012 Oct 15;22(20):6429-32. doi: 10.1016/j.bmcl.2012.08.061. Epub 2012 Aug 23.

Abstract

In an attempt to identify new potential lead as antimicrobial agent, twenty hybrids of marine bromopyrrole alkaloids with 1,3,4-oxadiazole were designed based on molecular hybridization technique and synthesized. Synthesized molecules were evaluated for their antibacterial, antifungal and antitubercular activities. Hybrids 5d, 5i, 5j and 5k exhibited equivalent antibacterial activity (MIC of 1.56 μg/mL) compared with standard drug ciprofloxacin against Staphylococcus aureus and Escherichia coli. Equal antifungal activity (MIC of 1.56 μg/mL) was shown by of hybrids 5j, 5k and 7d compared with standard Amphotericin-B. The inhibition of Mycobacterium tuberculosis at concentrations as low as 1.6 and 1.5 μg/mL by compounds 5f and 7d respectively indicates that these compounds can act as leads for development of newer anti-TB compounds.

摘要

为了寻找新的潜在抗菌药物先导化合物,我们运用分子杂交技术设计并合成了 20 种海洋溴代吡咯生物碱与 1,3,4-噁二唑的杂合化合物。对合成的分子进行了抗菌、抗真菌和抗结核活性评估。与标准药物环丙沙星相比,化合物 5d、5i、5j 和 5k 对金黄色葡萄球菌和大肠杆菌具有等效的抗菌活性(MIC 为 1.56μg/mL)。与标准两性霉素 B 相比,杂合化合物 5j、5k 和 7d 表现出相同的抗真菌活性(MIC 为 1.56μg/mL)。化合物 5f 和 7d 的浓度分别低至 1.6 和 1.5μg/mL 时即可抑制结核分枝杆菌,这表明这些化合物可以作为开发新型抗结核化合物的先导化合物。

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