Synthesis and anti-Candidal activity of N-(4-aryl/cyclohexyl)-2-(pyridine-4-yl carbonyl) hydrazinecarbothioamide

被引:23
作者
Bhat, Mashooq Ahmad [1 ]
Khan, Abdul Arif [2 ]
Khan, Shahanavaj [2 ]
Al-Omar, Mohamed A. [1 ]
Parvez, Mohammad Khalid [3 ]
Al-Dosari, Mohammed Salem [3 ]
Al-Dhfyan, Abdullah [4 ]
机构
[1] King Saud Univ, Dept Pharmaceut Chem, Coll Pharm, Riyadh 11451, Saudi Arabia
[2] King Saud Univ, Dept Pharmaceut, Coll Pharm, Riyadh 11451, Saudi Arabia
[3] King Saud Univ, Dept Pharmacognosy, Coll Pharm, Riyadh 11451, Saudi Arabia
[4] King Faisal Specialized Hosp & Res Ctr, Stem Cell & Tissue Re Engn Program, Res Ctr, Riyadh 11211, Saudi Arabia
关键词
Thiosemicarbazide; Isoniazid; In vitro anti-Candidal activity; Candida spp; Cytotoxicity; ANTIMICROBIAL ACTIVITY; BIOLOGICAL EVALUATION; STRUCTURE ELUCIDATION; EPIDEMIOLOGY; DERIVATIVES; CYTOTOXICITY; INFECTIONS; ANTIFUNGAL; INHIBITORS; DISCOVERY;
D O I
10.1016/j.bmcl.2014.01.060
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Eighteen N-(4-aryl/cyclohexyl)-2-(pyridine-4-yl carbonyl) hydrazinecarbothioamide derivatives were synthesized, evaluated against ten clinical isolates of Candida spp. and compared with itraconazole. Introduction of p-chloro (2c), p-iodo (2q), m-chloro (2l) and o-nitro (2r) substitution at phenyl ring of thiosemicarbazide enhanced the anti-Candida activity. Compound (2c) bearing p-cholorophenyl ring was found to be the most effective against Candida albicans ATCC 66027, Candida spp. 12810 (blood) and Candida spp. 178 (HVS) with MIC value of 0.09-0.78 mu g/mL, whereas itraconazole exhibits the inhibitory activity with MIC value of 0.04-1.56 mu g/mL against all tested strains. There is a correlation between anti-Candidal activity and p-chloro substitution at phenyl ring of thiosemicarbazide. All synthesized compounds were investigated for their potential cytotoxicity against non cancer cell line MCF-10A. The active compounds 2c, 2r and 2a were further investigated for their cytotoxic effects on three cancer cell lines; HT1080 (skin), HepG2 (liver) and A549 (lung). The active compounds showed minimal cytotoxic activity against non cancer cell line and all three cancer cell lines. Moreover, compound 2c displaying better activity against C. albicans ATCC66027 and Candida spp. [blood] compared to reference drug (itraconazole), represents a good lead for the development of newer, potent and broad spectrum anti-Candidal agents. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1299 / 1302
页数:4
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