title: Design, synthesis and biological evaluation of 2-mercapto-3-phenethylquinazoline bearing anilide fragments as potential antitumor agents: molecular docking study.
abstract: A novel series of 2-(3-phenethyl-4(3H)quinazolin-2-ylthio)-N-substituted anilide and substituted phenyl 2-(3-phenethyl-4(3H) quinazolin-2-ylthio)acetate were designed, synthesized and evaluated for their in-vitro antitumor activity. Compound 15 possessed remarkable broad-spectrum antitumor activity which almost sevenfold more active than the known drug 5-FU with GI50 values of 3.16 and 22.60 μM, respectively. Compound 15 exhibited remarkable growth inhibitory activity pattern against renal cancer (GI50=1.77 μM), colon cancer (GI50=2.02 μM), non-small cell lung cancer (GI50=2.04 μM), breast cancer (GI50=2.77 μM), ovarian cancer (GI50=2.55 μM) and melanoma cancer (GI50=3.30 μM). Docking study was performed for compound 15 into ATP binding site of EGFR-TK which showed similar binding mode to erlotinib.
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Al-Suwaidan
authors.forename: Amer M
authors.initials: AM
authors.lastname: Alanazi
authors.forename: Alaa A-M
authors.initials: AA
authors.lastname: Abdel-Aziz
authors.forename: Menshawy A
authors.initials: MA
authors.lastname: Mohamed
authors.forename: Adel S
authors.initials: AS
authors.lastname: El-Azab
mesh_terms: D000813:Anilides / Q000737:chemistry*; D000970:Antineoplastic Agents / 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; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D011799:Quinazolines; D013438:Sulfhydryl Compounds