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

摘要

Abstract 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-l ) 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?μg/mL) and (MIC: 0.49–0.98?μg/mL) respectively and antimycobacterial activity (MIC?=?0.76 and 0.39?μg/mL) respectively. Besides, several derivatives, 6e , 6h , 6l-6o , 6q , 6r , 12a , 12b , 12e , 12h , 12k and 12l , exhibited significant antibacterial and antifungal activities with MIC values ranging from 1.95 to 7.81?μg/mL, they also displayed excellent to good activity against Mycobacterium tuberculosis with MIC range from 0.39 to 3.12?μg/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. Graphical abstract Compounds 6o , 6p , and 6r displayed superior antimycobacterial (MIC?=?0.39?μg/mL) and antimicrobial (MICs?=?0.49–3.9?μg/mL) activities. Compounds 6e , 6f , 6l and 6n showed very good antimycobacterial activities with MIC 0.78?μg/mL and good antimicrobial activity MICs?=?0.49–15.63?μg/mL. Display Omitted Highlights ? A novel series of pyridine and quinolone derivatives have been synthesized and evaluated as antimicrobial and antimycobacterial agents. ? A SAR was discussed and a QSAR study was carried out to correlate this activity.