Synthesis, structure-activity relationships, and in vitro antibacterial and antifungal activity evaluations of novel pyrazole carboxylic and dicarboxylic acid derivatives
Synthesis, structure-activity relationships, and in vitro antibacterial and antifungal activity evaluations of novel pyrazole carboxylic and dicarboxylic acid derivatives
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DOI：
10.1016/j.ejmech.2014.03.033
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发表时间：
2014-05-06
影响因子：
6.7
通讯作者：
Ok, Salim
中科院分区：
文献类型：
--
作者：
Mert, Samet;Kasimogullari, Rahmi;Ok, Salim
合成了一系列吡唑-3-羧酸和3，4-吡唑-3，4-二羧酸衍生物，其结构经核磁共振(H-1和C-13)、红外光谱和元素分析确证。采用改良琼脂扩散法筛选化合物对5种细菌和5种真菌病原菌的抑菌和抗真菌活性。大多数分子对标准株和临床株的白色念珠菌均有抑制作用。然而，只有分子8、10、21和22对近缘念珠菌、热带假丝酵母菌和光滑假丝酵母菌有一定的抑制作用。用电子构象方法研究了化合物对白色念珠菌的构效关系。通过对白念珠菌活性片段的电子学和几何特征分析，得到了对白念珠菌具有抑制和非抑制作用的药效团和抗药团。这些片段和相关参数可用于设计未来更有效的抗真菌药物。研究表明，F和O等电负性原子在吡唑取代基上的位置以及这些原子上的结合电荷量对调节白色念珠菌的抗真菌活性是至关重要的。(C)2014年爱思唯尔·马森公司。版权所有。
A series of pyrazole-3-carboxylic acid and pyrazole-3,4-dicarboxylic acid derivatives were synthesized, the structures were confirmed by their NMR (H-1 and C-13) and FT-IR spectra, and elemental analyses. The antibacterial and antifungal activities of the compounds against five bacterial and five fungal pathogens were screened using modified agar well diffusion assay. Most of the molecules have inhibitory effects on both standard and clinical Candida albicans strains. However, only the molecules 8, 10, 21, and 22 demonstrate some inhibitory effects on Candida parapsilosis, Candida tropicalis, and Candida glabrata strains. The structure-antifungal activity relationships of the compounds on the C. albicans strains were investigated by electron-conformational method. The pharmacophores and antipharmacophores responsible for the inhibition and non-inhibition of the C. albicans strains were obtained by electronic and geometrical characteristics of the reactive fragments of the molecules. These fragments along with the associated parameters can be used in designing the future more potent antifungal agents. It has been shown that both the positions of electronegative atoms like F and O in the pyrazole substituents and the amount of the associated charges on such atoms are crucial in regulating the strength of antifungal activity for the C. albicans strain. (C) 2014 Elsevier Masson SAS. All rights reserved.