title: Design, synthesis and molecular modelling studies of novel 3-acetamido-4-methyl benzoic acid derivatives as inhibitors of protein tyrosine phosphatase 1B.
abstract: A novel series of 3-acetamido-4-methyl benzoic acid derivatives designed on the basis of vHTS hit ZINC02765569 were synthesized and screened for PTP1B inhibitory activity. The most potent compounds 3-(1-(5-methoxy-1H-benzo[d]imidazol-2-ylthio)acetamido)-4-methyl benzoic acid (10c, IC₅₀ 8.2 μM) and 3-(2-(benzo[d]thiazol-2-ylthio)acetamido)-4-methyl benzoic acid (10e, IC₅₀ 8.3 μM) showed maximum PTP1B inhibitory activity. Docking studies were also performed to understand the nature of interactions governing the binding mode of the designed molecules within the active site of the PTP1B enzyme.
authors.affiliation: CADD Laboratory, School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Airport Bypass Road, Gandhi Nagar, Bhopal, MP 462036, India.
authors.forename: Monika
authors.initials: M
authors.lastname: Rakse
authors.forename: Chandrabose
authors.initials: C
authors.lastname: Karthikeyan
authors.forename: Girdhar Singh
authors.initials: GS
authors.lastname: Deora
authors.forename: N S H N
authors.initials: NS
authors.lastname: Moorthy
authors.forename: Vandana
authors.initials: V
authors.lastname: Rathore
authors.forename: Arun K
authors.initials: AK
authors.lastname: Rawat
authors.forename: A K
authors.initials: AK
authors.lastname: Srivastava
authors.forename: Piyush
authors.initials: P
authors.lastname: Trivedi
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001565:Benzoates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C000591486:3-acetamido-4-methyl benzoic acid; D000081:Acetamides; D000970:Antineoplastic Agents; D001565:Benzoates; D004791:Enzyme Inhibitors; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Acetamido benzoic acid derivatives; Diabetes; Lead optimization; Molecular modelling; PTP1B