الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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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.