الفهرس | Only 14 pages are availabe for public view |
Abstract The treatment of infectious diseases still remain as a serious public health problem because of a combination of factors including emerging infectious diseases and the increasing number of multi-drug resistant microbial pathogens with particular relevance for Gram negative bacteria and mycobacterium tuberculosis. The therapeutic problem has achieved increasing i mportance in hospitalised patients, in immune suppressed patients with AIDS or undergoing anticancer therapy and organ transplants. The increased development of highly resistant bacterial strains and tuberculosis, highlighting the urgent need of novel antibacterial and antimycobacterial agents. In this work, two novel series of nicotinic acid hydrazone derivatives (VIa-r) and quinolone hydrazide derivatives (XIIa-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 VIf and VIp bearing the 3,4,5-(OCH 3 ) 3 and 2,5-(OCH 3 ) 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, VIe, VIh, VIl- VIo, VIq, VIr, XIIa, XIIb, XIIe, XIIh, XIIk and XIIl, 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. Synthesis of the designed compounds was then accomplished & their structures were confirmed by various spectral and microanalytical data. |