title: Synthesis, screening and docking analysis of hispolon analogs as potential antitubercular agents.
abstract: A series of 20 hispolons/dihydrohispolons were synthesized and characterized by spectral data. These compounds were subjected to in vitro antitubercular activity screening against Mycobacterium tuberculosis (H37Rv) strain. The synthesized compounds showed varied antitubercular activity ranging from 100 to 1.6μg/mL. Among the screened compounds, four compounds (H1, H2, H3 and H15) have shown moderate activity with MIC 25μg/mL. Potent activities were observed for the dihydrohispolon derivative H14 (MIC 1.6μg/mL) followed by H13 (6.25μg/mL) and H17 (12.5μg/mL), H19 (3.125μg/ML). Docking simulations gave good insights on the possible interactions between the tested compounds and β-keto acyl synthase enzyme (mtbFabH). Drug-inhibitor combination studies showed no synergism with the drugs targeting mycolic acid biosynthesis (isoniazid, ethambutol and thiolactomycin, a specific inhibitor of KAS-B enzyme) but showed significant synergism with other drugs including rifampicin and ciprofloxacin ascertaining the drug target for hispolons as inhibition of mycolic acid biosynthesis, probably via mtbFabH.
authors.affiliation: Department of Chemistry, Acharya Nagarjuna University, Guntur, AP, India.
authors.forename: Neduri V
authors.initials: NV
authors.lastname: Balaji
authors.affiliation: Department of Chemistry, Acharya Nagarjuna University, Guntur, AP, India. Electronic address: dr.b.haribabu@gmail.com.
authors.forename: Bollikolla
authors.initials: B
authors.lastname: Hari Babu
authors.affiliation: Natsol Laboratories Private Limited, II Floor, Research & Development Building, Ramky Commercial Hub, J.N. Pharmacity, Visakhapatnam, India.
authors.forename: Gottumukkala V
authors.initials: GV
authors.lastname: Subbaraju
authors.affiliation: Medicinal Chemistry Research Labs, College of Pharmaceutical Sciences, Andhra University, Visakhapatnam 530 003, India.
authors.forename: Kurre
authors.initials: K
authors.lastname: Purna Nagasree
authors.affiliation: Medicinal Chemistry Research Labs, College of Pharmaceutical Sciences, Andhra University, Visakhapatnam 530 003, India. Electronic address: drmmkau@gmail.com.
authors.forename: Muthyala
authors.initials: M
authors.lastname: Murali Krishna Kumar
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002396:Catechols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D002396:Catechols; C103442:hispolon
keywords: Antitubercular; Hispolons; Ketoacyl synthase docking analysis