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一些新型2-(取代苯基/苄基)-5-[(2-苯并呋喃基)甲酰胺基]苯并恶唑的合成、抗菌活性及药效团分析

Synthesis, antimicrobial activity, pharmacophore analysis of some new 2-(substitutedphenyl/benzyl)-5-[(2-benzofuryl)carboxamido]benzoxazoles.

作者信息

Alper-Hayta Sabiha, Arisoy Mustafa, Temiz-Arpaci Ozlem, Yildiz Ilkay, Aki Esin, Ozkan Semiha, Kaynak Fatma

机构信息

Ankara University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 06100 Tandogan, Ankara, Turkey.

出版信息

Eur J Med Chem. 2008 Nov;43(11):2568-78. doi: 10.1016/j.ejmech.2007.12.019. Epub 2007 Dec 31.

Abstract

The synthesis and antimicrobial activity of a new series of 2-(substitutedphenyl/benzyl)-5-[(2-benzofuryl)carboxamido]benzoxazole derivatives 3-12 were described. The in vitro antimicrobial activity of the compounds was determined against some Gram-positive, Gram-negative bacteria and fungi and their drug-resistant isolates in comparison with standard drugs. Antimicrobial results indicated that the synthesized compounds possessed a broad spectrum of activity with MIC values 500-15.625 microg/ml. In the series, the most active compound against Candida krusei and Candida albicans isolate is 8 with MIC value 31.25 microg/ml. However, it is one dilution less potent than the compared fluconazole. Some of the screened compounds exhibit significant activity, having MIC value as 31.25 microg/ml in Pseudomonas aeruginosa having same activity as Rifampicin. Furthermore, considering the worth of developing new antibacterial agents against drug-resistant P. aeruginosa the present study explores the structure-activity relationship analysis of 2-(substitutedphenyl/benzyl)-5-[(2-benzofuryl)carboxamido]benzoxazoles using 3D-common features pharmacophore hypotheses approach.

摘要

描述了一系列新的2-(取代苯基/苄基)-5-[(2-苯并呋喃基)甲酰胺基]苯并恶唑衍生物3-12的合成及其抗菌活性。与标准药物相比,测定了这些化合物对一些革兰氏阳性菌、革兰氏阴性菌和真菌及其耐药菌株的体外抗菌活性。抗菌结果表明,合成的化合物具有广谱活性,MIC值为500-15.625微克/毫升。在该系列中,对克鲁斯念珠菌和白色念珠菌分离株最具活性的化合物是8,MIC值为31.25微克/毫升。然而,它的效力比对照氟康唑低一个稀释度。一些筛选出的化合物表现出显著活性,在铜绿假单胞菌中的MIC值为31.25微克/毫升,与利福平具有相同活性。此外,考虑到开发针对耐药铜绿假单胞菌的新型抗菌剂的价值,本研究采用3D共同特征药效团假说方法探索了2-(取代苯基/苄基)-5-[(2-苯并呋喃基)甲酰胺基]苯并恶唑的构效关系分析。

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