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取代的3-((Z)-2-(4-硝基苯基)-2-(1H-四唑-5-基)乙烯基)-4H-色烯-4-酮作为新型抗耐甲氧西林金黄色葡萄球菌(MRSA)药物:合成、构效关系及体外评估

Substituted 3-((Z)-2-(4-nitrophenyl)-2-(1H-tetrazol-5-yl) vinyl)-4H-chromen-4-ones as novel anti-MRSA agents: synthesis, SAR, and in-vitro assessment.

作者信息

Diwakar Santosh D, Bhagwat Sachin S, Shingare Murlidhar S, Gill Charansing H

机构信息

Drug Discovery Research, Chemistry, Wockhardt Research Centre, D-4, MIDC, Chikalthana, Aurangabad 431 210, India.

出版信息

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4678-81. doi: 10.1016/j.bmcl.2008.07.007. Epub 2008 Jul 9.

Abstract

In search for a new antibacterial agent with improved antimicrobial spectrum and potency, we designed and synthesized a series of novel 3-((Z)-2-(4-nitrophenyl)-2-(1H-tetrazol-5-yl) vinyl)-4H-chromen-4-ones 7a-h by convergent synthesis approach. All the synthesized compounds were assayed for their in-vitro antibacterial activities against gram-negative and gram-positive bacteria. The preliminary structure-activity relationship, to elucidate the essential structure requirements for the antimicrobial activity that results into anti-MRSA (methicillin-resistant S. aureus) potential, has been described. Amongst the synthesized compounds 7d, 7e, 7f and 7h were found to possess activity against methicillin-resistant S. aureus in addition to the activity against other bacterial strains such as E. faecalis, S. pneumoniae, and E. coli.

摘要

为了寻找一种具有更广泛抗菌谱和更高效力的新型抗菌剂,我们采用汇聚合成法设计并合成了一系列新型的3-((Z)-2-(4-硝基苯基)-2-(1H-四氮唑-5-基)乙烯基)-4H-色烯-4-酮7a-h。对所有合成的化合物进行了针对革兰氏阴性菌和革兰氏阳性菌的体外抗菌活性测定。已经描述了初步的构效关系,以阐明导致抗耐甲氧西林金黄色葡萄球菌(MRSA)潜力的抗菌活性的基本结构要求。在合成的化合物中,发现7d、7e、7f和7h除了对粪肠球菌、肺炎链球菌和大肠杆菌等其他细菌菌株具有活性外,还对耐甲氧西林金黄色葡萄球菌具有活性。

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