title: Design, synthesis and antimycobacterial activity of various 3-(4-(substitutedsulfonyl)piperazin-1-yl)benzo[d]isoxazole derivatives.
abstract: In this communication, we synthesized a series of twenty four novel 3-(4-(substitutedsulfonyl)piperazin-1-yl)benzo[d]isoxazole analogues, characterized using various spectroscopic techniques and evaluated for their in vitro anti-tubercular activity against Mycobacterium tuberculosis (MTB) H37Rv strain. The titled compounds exhibited Minimum inhibitory concentration (MIC) between 3.125 and >50 μg/mL. Among the tested compounds, 5c, 6a, 6j and 6p exhibited moderate activity (MIC = 12.5 μg/mL), while 5a and 6i exhibited good activity (MIC = 6.25 μg/mL) and 6b (MIC = 3.125 μg/mL) exhibited very good anti-tubercular activity. In addition, the analogues 5a, 5c, 6a, 6b, 6i, 6j and 6p were subjected to toxicity studies against mouse macrophage (RAW 264.7) cell lines to analyse the selectivity profile of the newly synthesized compounds and selectivity index of the most active compound was found to be >130 indicating suitability of the compound for further drug development. Structure of 6b was further substantiated through single crystal XRD.
authors.affiliation: Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, Telangana, India.
authors.forename: Kalaga Mahalakshmi
authors.initials: KM
authors.lastname: Naidu
authors.affiliation: Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, Telangana, India.
authors.forename: Amaroju
authors.initials: A
authors.lastname: Suresh
authors.affiliation: Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, Telangana, India.
authors.forename: Jayanty
authors.initials: J
authors.lastname: Subbalakshmi
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, Telangana, India.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, Telangana, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch 7707, Cape Town, South Africa.
authors.forename: Pallepogu
authors.initials: P
authors.lastname: Raghavaiah
authors.affiliation: Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, Telangana, India. Electronic address: kvgc@hyderabad.bits-pilani.ac.in.
authors.forename: Kondapalli Venkata Gowri
authors.initials: KV
authors.lastname: Chandra Sekhar
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D015195:Drug Design; D007555:Isoxazoles / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D007555:Isoxazoles; D010879:Piperazines
keywords: Antimycobacterial activity; Benzo[d]isoxazole; Mycobacterium tuberculosis; Piperazine sulphonamide