Antitumor evaluation and molecular docking study of substituted 2-benzylidenebutane-1,3-dione, 2-hydrazonobutane-1,3-dione and trifluoromethyl-1H-pyrazole analogues

作者：Al Suwaidan Ibrahim A; Abdel Aziz Naglaa I; El Azab Adel S; El Sayed Magda A A; Alanazi Amer M; El Ashmawy Mahmoud B; Abdel Aziz Alaa A M^*

来源：Journal of Enzyme Inhibition and Medicinal Chemistry, 2015, 30(4): 679-687.

DOI：10.3109/14756366.2014.960863

• Antitumor activity
• chalcones
• hydrazones
• molecular docking
• pyrazoles

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-pyrazol4-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 GI(50,) (6.61 and 22.60 mu M), TGI (42.66 and <100 mu M) and LC50 (93.33 and <100 mu M) 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.

• 出版日期2015-8