title: Synthesis, biological evaluation and molecular docking study of some novel indole and pyridine based 1,3,4-oxadiazole derivatives as potential antitubercular agents.
abstract: A series of indole and pyridine based 1,3,4-oxadiazole derivatives 5a-t were synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG both in active and dormant state. Compounds 5b, 5e, 5g and 5q exhibited very good antitubercular activity. All the newly synthesized compounds 5a-t were further evaluated for anti-proliferative activity against HeLa, A549 and PANC-1 cell lines using modified MTT assay and found to be noncytotoxic. On the basis of cytotoxicity and MIC values against Mycobacterium bovis BCG, selectivity index (SI) of most active compounds 5b, 5e, 5g and 5q was calculated (SI=GI50/MIC) in active and dormant state. Compounds 5b, 5e and 5g demonstrated SI values ⩾10 against all three cell lines and were found to safe for advance screening. Compounds 5a-t were further screened for their antibacterial activity against four bacteria strains to assess their selectivity towards MTB. In addition, the molecular docking studies revealed the binding modes of these compounds in active site of enoyl reductase (InhA), which in turn helped to establish a structural basis of inhibition of mycobacteria. The potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for further optimization.
authors.affiliation: Division of Medicinal Chemistry, Department of Chemistry (DST-FIST Sponsored), Mahatma Gandhi Campus, Maharaja Krishnakumarsinhji Bhavnagar University, Bhavnagar 364 002, Gujarat, India. Electronic address: dnisheeth@rediffmail.com.
authors.forename: N C
authors.initials: NC
authors.lastname: Desai
authors.affiliation: Division of Medicinal Chemistry, Department of Chemistry (DST-FIST Sponsored), Mahatma Gandhi Campus, Maharaja Krishnakumarsinhji Bhavnagar University, Bhavnagar 364 002, Gujarat, India.
authors.forename: Hardik
authors.initials: H
authors.lastname: Somani
authors.affiliation: Division of Medicinal Chemistry, Department of Chemistry (DST-FIST Sponsored), Mahatma Gandhi Campus, Maharaja Krishnakumarsinhji Bhavnagar University, Bhavnagar 364 002, Gujarat, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Trivedi
authors.affiliation: Division of Medicinal Chemistry, Department of Chemistry (DST-FIST Sponsored), Mahatma Gandhi Campus, Maharaja Krishnakumarsinhji Bhavnagar University, Bhavnagar 364 002, Gujarat, India.
authors.forename: Kandarp
authors.initials: K
authors.lastname: Bhatt
authors.affiliation: Combi Chem Bio Resource Centre, National Chemical Laboratory, Pune 411 008, India.
authors.forename: Laxman
authors.initials: L
authors.lastname: Nawale
authors.affiliation: Combi Chem Bio Resource Centre, National Chemical Laboratory, Pune 411 008, India.
authors.forename: Vijay M
authors.initials: VM
authors.lastname: Khedkar
authors.affiliation: School of Chemical Sciences, Central University of Gujarat, Sector-30, Gandhinagar 382 030, Gujarat, India.
authors.forename: Prakash C
authors.initials: PC
authors.lastname: Jha
authors.affiliation: Combi Chem Bio Resource Centre, National Chemical Laboratory, Pune 411 008, India.
authors.forename: Dhiman
authors.initials: D
authors.lastname: Sarkar
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D009163:Mycobacterium bovis / Q000187:drug effects* / Q000201:enzymology; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology; D010069:Oxadiazoles / Q000737:chemistry* / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary
chemical_list: D000995:Antitubercular Agents; D007211:Indoles; D010069:Oxadiazoles; D011725:Pyridines; C583463:1,3,4-oxadiazole
keywords: 1,3,4-Oxadiazole; Antitubercular activity; Cytotoxicity; Indole; Molecular docking; Pyridine