title: Design, synthesis, in silico and in vitro studies of novel 4-methylthiazole-5-carboxylic acid derivatives as potent anti-cancer agents.
abstract: Since inhibitors of mucin onco proteins are potential targets for breast cancer therapy, a series of novel 4-methylthiazole-5-carboxylic acid (1) derivatives 3a-k were synthesized by the reaction of 1 with SOCl2 followed by different bases/alcohols in the presence of triethylamine. Once synthesized and characterized, their binding modes with MUC1 were studied by molecular docking analysis using Aruglab 4.0.1 and QSAR properties were determined using HyperChem. All synthesized compounds were screened for in vitro anti-breast cancer activity against MDA-MB-231 breast adenocarcinoma cell lines by Trypan-blue cell viability assay and MTT methods. Compounds 1, 3b, 3d, 3e, 3i and 3f showed good anti-breast cancer activity. Since 1 and 3d exhibited high potent activity against MDA-MB-231 cell lines, they show could be effective mucin onco protein inhibitors.
authors.affiliation: Department of Chemistry, Sri Venkateswara University, Tirupati 517502, India; Mylan Laboratories Ltd, CRD, Anrich Industrial Estate, Bollaram, Hyderabad 502325, India.
authors.forename: Ravendra Babu
authors.initials: RB
authors.lastname: Kilaru
authors.affiliation: Department of Chemistry, Sri Venkateswara University, Tirupati 517502, India; Department of Pharmacology & Toxicology and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, Lawrence, KS 66047, United States.
authors.forename: Koteswara Rao
authors.initials: KR
authors.lastname: Valasani
authors.affiliation: Division of Animal Biotechnology, Department of Zoology, Sri Venkateswara University, Tirupati 517502, India.
authors.forename: Nanda Kumar
authors.initials: NK
authors.lastname: Yellapu
authors.affiliation: Department of Pathology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Hari Prasad
authors.initials: HP
authors.lastname: Osuru
authors.affiliation: Department of Chemistry, Sri Venkateswara University, Tirupati 517502, India.
authors.forename: Chandra Sekhar
authors.initials: CS
authors.lastname: Kuruva
authors.affiliation: Division of Animal Biotechnology, Department of Zoology, Sri Venkateswara University, Tirupati 517502, India.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Matcha
authors.affiliation: Department of Chemistry, Sri Venkateswara University, Tirupati 517502, India. Electronic address: rajuchamarthi10@gmail.com.
authors.forename: Naga Raju
authors.initials: NR
authors.lastname: Chamarthi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000596735:4-methylthiazole-5-carboxylic acid; D000970:Antineoplastic Agents; D013844:Thiazoles
keywords: 4-methylthiazole-5-carboxylic acid derivatives; Breast cancer; Molecular docking; Mucin; QSAR