title: Design, synthesis and anti-tubercular evaluation of new 2-acylated and 2-alkylated amino-5-(4-(benzyloxy)phenyl)thiophene-3-carboxylic acid derivatives. Part 1.
abstract: A series of 2-acylated and 2-alkylated amino-5-(4-(benzyloxy)phenyl)thiophene-3-carboxylic acid derivatives were synthesized and evaluated for anti-tubercular activity. Among these compounds, 10d, 15, 12h and 12k inhibited Mycobacterium tuberculosis (Mtb) growth with MIC values between 1.9 and 7.7 μM and low toxicity against VERO cells. The four compounds were also tested against multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) clinical strains, which were found to show moderate activity. In addition, molecular docking simulation was performed to position compounds 10d, 15, 12h and 12k into mtFabH active site to predict the probable binding mode. These studies thus suggest that the designed 2-amino-5-phenylthiophene-3-carboxylic acid scaffold may serve as new promising template for further elaboration as anti-TB drugs.
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Lu
authors.forename: Baojie
authors.initials: B
authors.lastname: Wan
authors.forename: Scott G
authors.initials: SG
authors.lastname: Franzblau
authors.forename: Qidong
authors.initials: Q
authors.lastname: You
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry*; D002522:Chlorocebus aethiops; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D021241:Spectrometry, Mass, Electrospray Ionization; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D000995:Antitubercular Agents; D002264:Carboxylic Acids; D013876:Thiophenes