title: A robust synthesis of functionalized 2H-indazoles via solid state melt reaction (SSMR) and their anti-tubercular activity.
abstract: A facile and convenient approach has been developed for the synthesis of functionalized indazoles via solid state melt reaction using easily accessible starting materials under catalyst-free conditions. This transformation involves electrocyclization via a conjugated nitrene intermediate obtained under thermal conditions. Further anti-tubercular activity screening of the molecules was undertaken, among the compounds 3a-3x screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv, compound 3u (MIC: 4.20μM) was found to be most active and are superior over existing standard drugs ciprofloxacin and ethambutol. Compounds 3c and 3x were found to equally potent as ethambutol. Among most potent compounds in the series, four compounds (3n, 3o, 3p and 3u) showed lower cytotoxicity which could be promising drug candidates for further development.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, Medak District 502285, Telangana, India.
authors.forename: Shinde
authors.initials: S
authors.lastname: Vidyacharan
authors.affiliation: Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, Medak District 502285, Telangana, India.
authors.forename: Chandan
authors.initials: C
authors.lastname: Adhikari
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, India.
authors.forename: Vagolu Siva
authors.initials: VS
authors.lastname: Krishna
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, India.
authors.forename: Rudraraju Srilakshmi
authors.initials: RS
authors.lastname: Reshma
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, India.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
authors.affiliation: Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, Medak District 502285, Telangana, India. Electronic address: sharada@iith.ac.in.
authors.forename: Duddu S
authors.initials: DS
authors.lastname: Sharada
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D002939:Ciprofloxacin / Q000494:pharmacology; D004977:Ethambutol / Q000494:pharmacology; D007191:Indazoles / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D007538:Isoniazid / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D012293:Rifampin / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D007191:Indazoles; D002939:Ciprofloxacin; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin
keywords: Cytotoxicity; Functionalized 2H-indazoles; Solid state melt reaction; Tuberculosis