title: Antitumor evaluation and molecular docking study of substituted 2-benzylidenebutane-1,3-dione, 2-hydrazonobutane-1,3-dione and trifluoromethyl-1H-pyrazole analogues.
abstract: A series of 2-(arylidene)-1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-diones (2-4), 4-(arylidene)-3-(4-chlorophenyl)-5-(trifluoromethyl)-4H-pyrazoles (5-7), 1-(4-chlorophenyl)-4,4,4-trifluoro-2-(2-(aryl)hydrazono)butane-1,3-diones (8, 9), 3-(4-chlorophenyl)-4-(2-(aryl)hydrazono)-5-(trifluoromethyl)-4H-pyrazoles (10, 11), 2-((3-(4-chlorophenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)methylene)malononitrile (13), 2-((5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)methylene)cycloalkan-1-ones (14, 15) and 1-(aryl)-3-(5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)prop-2-en-1-ones (16, 17) were designed, synthesized and evaluated for their in vitro antitumor activity. 1-(4-Chlorophenyl)-4,4,4-trifluoro-2-(2-(4-methoxyphenyl)hydrazono)butane-1,3-dione (8) showed potential and broad spectrum antitumor activity compared to the known drug 5-FU with GI50, (6.61 and 22.60 µM), TGI (42.66 and <100 µM) and LC50 (93.33 and <100 µM) values, respectively. On the other hand, compound 8 yielded selective activities toward melanoma, colon, non-small lung and breast cancer cell lines compared with erlotinib and gefitinib. Molecular docking methodology was performed for compound 8 into binding site of B-RAFV600E and EGFR kinases which showed similar binding mode to vemurafenib (PLX4032) and erlotinib, respectively.
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University , Riyadh , Saudi Arabia .
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Al-Suwaidan
authors.forename: Naglaa I
authors.initials: NI
authors.lastname: Abdel-Aziz
authors.forename: Adel S
authors.initials: AS
authors.lastname: El-Azab
authors.forename: Magda A-A
authors.initials: MA
authors.lastname: El-Sayed
authors.forename: Amer M
authors.initials: AM
authors.lastname: Alanazi
authors.forename: Mahmoud B
authors.initials: MB
authors.lastname: El-Ashmawy
authors.forename: Alaa A-M
authors.initials: AA
authors.lastname: Abdel-Aziz
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles
keywords: Antitumor activity; chalcones; hydrazones; molecular docking; pyrazoles