title: Seeking potent anti-tubercular agents: Design, synthesis, anti-tubercular activity and docking study of various ((triazoles/indole)-piperazin-1-yl/1,4-diazepan-1-yl)benzo[d]isoxazole derivatives.
abstract: A series of thirty eight novel 3-(4-((substituted-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl/1,4-diazepan-1-yl)benzo[d]isoxazole and 1-(4-(benzo[d]isoxazol-3-yl)piperazin-1-yl/1,4-diazepan-1-yl)-2-(1H-indol-3-yl)substituted-1-one analogues were synthesised, characterised using various analytical techniques and evaluated for in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain and two 'wild' strains Spec. 210 and Spec. 192. The titled compounds exhibited minimum inhibitory concentration (MIC) ranging from 6.16 to >200μM. Among the tested compounds, 7i, 7y and 7z exhibited moderate activity (MIC=24.03-29.19μM) and 7j exhibited very good anti-tubercular activity (MIC=6.16μM). Furthermore, 7i, 7j, 7y and 7z were found to be non-toxic against mouse macrophage cell lines when screened for toxicity. All the synthesised compounds were docked to pantothenate synthetase enzyme site to know deferent binding interactions with the receptor.
authors.affiliation: Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, 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, India.
authors.forename: Singireddi
authors.initials: S
authors.lastname: Srinivasarao
authors.affiliation: Microbiology Department, National Tuberculosis and Lung Diseases Research Institute, 01-138 Warsaw, Poland.
authors.forename: Napiórkowska
authors.initials: N
authors.lastname: Agnieszka
authors.affiliation: Microbiology Department, National Tuberculosis and Lung Diseases Research Institute, 01-138 Warsaw, Poland.
authors.forename: Augustynowicz-Kopeć
authors.initials: AK
authors.lastname: Ewa
authors.affiliation: College of Pharmaceutical Sciences, Andhra University, Visakhapatnam 530003, India.
authors.forename: Muthyala Murali Krishna
authors.initials: MM
authors.lastname: Kumar
authors.affiliation: Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad 500 078, India. Electronic address: kvgc@hyderabad.bits-pilani.ac.in.
authors.forename: Kondapalli Venkata Gowri
authors.initials: KV
authors.lastname: Chandra Sekhar
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D007555:Isoxazoles / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation
chemical_list: D000995:Antitubercular Agents; D007555:Isoxazoles
keywords: Anti-tubercular agents; Benzo[d]isoxazole; Homopiperazine; Indole; Mycobacterium tuberculosis; Piperazine; Triazole