title: An efficient synthesis and biological screening of benzofuran  and benzo[d]isothiazole derivatives for Mycobacterium tuberculosis  DNA GyrB inhibition.
abstract: A series of twenty eight molecules of ethyl 5-(piperazin-1-yl)benzofuran-2-carboxylate and 3-(piperazin-1-yl)benzo[d]isothiazole were designed by molecular hybridization of thiazole aminopiperidine core and carbamide side chain in eight steps and were screened for their in vitro Mycobacterium smegmatis (MS) GyrB ATPase assay, Mycobacterium tuberculosis (MTB) DNA gyrase super coiling assay, antitubercular activity, cytotoxicity and protein-inhibitor interaction assay through differential scanning fluorimetry. Also the orientation and the ligand-protein interactions of the top hit molecules with MS DNA gyrase B subunit active site were investigated applying extra precision mode (XP) of Glide. Among the compounds studied, 4-(benzo[d]isothiazol-3-yl)-N-(4-chlorophenyl)piperazine-1-carboxamide (26) was found to be the most promising inhibitor with an MS GyrB IC50 of 1.77 ± 0.23 μM, 0.42 ± 0.23 against MTB DNA gyrase, MTB MIC of 3.64 μM, and was not cytotoxic in eukaryotic cells at 100 μM. Moreover the interaction of protein-ligand complex was stable and showed a positive shift of 3.5 °C in differential scanning fluorimetric evaluations
authors.affiliation: Department of Chemistry, Sri Krishnadevaraya University, Anantapur 515055, India.
authors.forename: Kummetha Indrasena
authors.initials: KI
authors.lastname: Reddy
authors.affiliation: Department of Chemistry, Sri Krishnadevaraya University, Anantapur 515055, India.
authors.forename: Konduri
authors.initials: K
authors.lastname: Srihari
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawaharnagar, Shameerpet, Hyderabad 500078, India.
authors.forename: Janupally
authors.initials: J
authors.lastname: Renuka
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawaharnagar, Shameerpet, Hyderabad 500078, India.
authors.forename: Komanduri Shruthi
authors.initials: KS
authors.lastname: Sree
authors.affiliation: Department of Chemistry, Sri Krishnadevaraya University, Anantapur 515055, India.
authors.forename: Aruna
authors.initials: A
authors.lastname: Chuppala
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawaharnagar, Shameerpet, Hyderabad 500078, India.
authors.forename: Variam Ullas
authors.initials: VU
authors.lastname: Jeankumar
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawaharnagar, Shameerpet, Hyderabad 500078, India.
authors.forename: Jonnalagadda Padma
authors.initials: JP
authors.lastname: Sridevi
authors.affiliation: Department of Chemistry, Sri Krishnadevaraya University, Anantapur 515055, India.
authors.forename: Kondra Sudhakar
authors.initials: KS
authors.lastname: Babu
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawaharnagar, Shameerpet, Hyderabad 500078, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawaharnagar, Shameerpet, Hyderabad 500078, India. Electronic address: dsriram@hyderabad.bits-pilani.ac.in.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D027081:DNA Gyrase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology*; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000601693:4-(benzo(d)isothiazol-3-yl)-N-(4-chlorophenyl)piperazine-1-carboxamide; D000995:Antitubercular Agents; D001572:Benzofurans; D052160:Benzothiazoles; D010879:Piperazines; D059005:Topoisomerase II Inhibitors; D027081:DNA Gyrase; C105430:benzofuran