title: Synthesis and bioactivity of novel triazole incorporated benzothiazinone derivatives as antitubercular and antioxidant agent.
abstract: In search of new active molecules against Mycobacterium tuberculosis (MTB) H37Ra and M. bovis BCG, a small focused library of benzothiazinone based 1,2,3-triazoles has been efficiently prepared via click chemistry approach. Several derivatives were found to be promising inhibitors of MTB and M. bovis BCG characterized by lower MIC values (27.34-29.37μg/mL). Among all the synthesized compounds, 6c and 6e is the most active compound against MTB and M. bovis BCG. The compounds were further tested for anti-proliferative activity against HeLa, A549 and A431 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antioxidant activity with IC50 range=14.14-47.11μg/mL. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target MTB DprE1, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of the in vitro and in silico study suggest that the triazole incorporated benzothiazinone may possess the ideal structural requirements for further development of novel therapeutic agents.
authors.affiliation: Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431 004, India.
authors.forename: Mubarak H
authors.initials: MH
authors.lastname: Shaikh
authors.affiliation: Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431 004, India.
authors.forename: Dnyaneshwar D
authors.initials: DD
authors.lastname: Subhedar
authors.affiliation: Combi Chem Bio Resource Centre, National Chemical Laboratory, Pune 411 008, India.
authors.forename: Manisha
authors.initials: M
authors.lastname: Arkile
authors.affiliation: Combi Chem Bio Resource Centre, National Chemical Laboratory, Pune 411 008, India; School of Health Sciences, University of KwaZulu Natal, Westville Campus, Durban 4000, South Africa.
authors.forename: Vijay M
authors.initials: VM
authors.lastname: Khedkar
authors.affiliation: Combi Chem Bio Resource Centre, National Chemical Laboratory, Pune 411 008, India.
authors.forename: Nandadeep
authors.initials: N
authors.lastname: Jadhav
authors.affiliation: Combi Chem Bio Resource Centre, National Chemical Laboratory, Pune 411 008, India.
authors.forename: Dhiman
authors.initials: D
authors.lastname: Sarkar
authors.affiliation: Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431 004, India. Electronic address: bapushingate@gmail.com.
authors.forename: Bapurao B
authors.initials: BB
authors.lastname: Shingate
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry; D045744:Cell Line, Tumor; D057930:Click Chemistry; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D009163:Mycobacterium bovis / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000995:Antitubercular Agents; D001426:Bacterial Proteins; D016166:Free Radical Scavengers; D013843:Thiazines; D014230:Triazoles; D000429:Alcohol Oxidoreductases; C583625:DprE1 protein, Mycobacterium tuberculosis
keywords: 1,2,3-Triazole; ADME prediction; Antioxidant; Antitubercular; Docking study