Synthesis, Biological Evaluation and Computational Study of New Quinoline Hybrids as Antitubercular Agent

Author(s): Zahid Zaheer*, Sameer I. Shaikh, Santosh N. Mokale, Deepak K. Lokwani

Journal Name: Letters in Drug Design & Discovery

Volume 15 , Issue 9 , 2018

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Graphical 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.

Keywords: Quinoline, antitubercular activity, antioxidant activity, cytotoxicity, molecular docking, pharmacophores.

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Article Details

Year: 2018
Published on: 16 July, 2018
Page: [914 - 922]
Pages: 9
DOI: 10.2174/1570180814666171026155930
Price: $65

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