Design, synthesis and 2D QSAR study of novel pyridine and quinolone hydrazone derivatives as potential antimicrobial and antitubercular agents

作者：Abdelrahman Mohamed A; Salama Ismail; Gomaa Mohamed S; Elaasser Mahmoud M; Abdel Aziz Marwa M; Soliman Dalia H^*

来源：European Journal of Medicinal Chemistry, 2017, 138: 698-714.

DOI：10.1016/j.ejmech.2017.07.004

• INH
• Quinolone
• Hydrazone
• Antimicrobial activity
• Antimycobacterial activity
• 2D-QSAR

The increased development of highly resistant bacterial strains and tuberculosis, constitute a serious public health threat, highlighting the urgent need of novel antibacterial agents. In this work, two novel series of nicotinic acid hydrazone derivatives (6a-r) and quinolone hydrazide derivatives (12a-1) were synthesized and evaluated as antimicrobial and antitubercular agents. The synthesized compounds were evaluated in vitro for their antibacterial, antifungal and antimycobacterial activities. Compounds 6f and 6p bearing the 3,4,5-(OCH3)3 and 2,5-(OCH3)2 benzylidene motifs were the most potent and as antibacterial, antifungal (MIC: 0.49-1.95 mu g/mL) and (MIC: 0.49-0.98 mu g/mL) respectively and antimycobacterial activity (MIC = 0.76 and 0.39 mu g/mL) respectively. Besides, several derivatives, 6e, 6h, 6I-6o, 6q, 6r, 12a, 12b, 12e, 12h, 12k and 121, exhibited significant antibacterial and antifungal activities with MIC values ranging from 1.95 to 7.81 mu g/mL, they also displayed excellent to good activity against Mycobacterium tuberculosis with MIC range from 039 to 3.12 mu g/mL. In addition, some of the most active compounds were tested for cytotoxic activities against human lung fibroblast normal cells (WI-38) and displayed low toxicity. Moreover, 2D-QSAR models to characterize the descriptors controlling the observed activities, were generated and validated.

• 出版日期2017-9-29