Title:Synthesis, Biological Evaluation and Computational Study of New Quinoline Hybrids as Antitubercular Agent
Volume: 15
Issue: 9
Author(s): Zahid Zaheer*, Sameer I. Shaikh, Santosh N. Mokale and Deepak K. Lokwani
Affiliation:
- Y. B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431001, (M.S.),India
Keywords:
Quinoline, antitubercular activity, antioxidant activity, cytotoxicity, molecular docking, pharmacophores.
Abstract: Background: Tuberculosis is global health threat caused by infectious bacillus called
Mycobacterium tuberculosis. To develop newer antitubercular agents against bacterial resistance,
we have designed new quinoline derivatives 6a-6f and 7a-7f by molecular hybridization approach
and evaluated for antitubercular, antioxidant and cytotoxicity studies along with molecular
docking study.
Methods: The designed molecules were synthesized by multi-step synthetic protocol and
structures of compounds were confirmed by NMR, Mass and Elemental analysis. The synthesized
derivatives were screened for antitubercular activity against Mycobacterium tuberculosis using
Microplate Alamar Blue Assay (MABA). The antioxidant activity and cytotoxicity were also
evaluated using 1,1-Dipheny-1-picrylhydrazyl (DPPH) radical scavenging and Sulforhodamine B
(SRB) assay, respectively. The molecular docking studies were performed in Glide v5.6
(Schrodinger).
Results: Among the synthesized derivatives, the compounds 6d and 7d displayed promising
antitubercular activity, with MIC value of 18.27 and 15.00 µM respectively and are relatively nontoxic
to HeLa cell line. The synthesized compounds were found to have potential antioxidant
activities with IC50 range of 73.47-123.46 µM. The molecular docking study, physicochemical and
pharmacokinetic properties prediction study suggested that the synthesized derivatives have
potential for development of good drug candidate.
Conclusion: Herein, we designed and synthesized a series of new quinoline pharmacophores
appended with isoniazid and linezolid-like fragment as a promising strategy for the development
of quinoline derivatives with potent biological activities.