Synthesis, characterization, in vitro DNA photocleavage and cytotoxicity studies of 4-arylazo-1-phenyl-3-(2-thienyl)-5-hydroxy-5-trifluoromethylpyrazolines and regioisomeric 4-arylazo-1-phenyl-5(3)-(2-thienyl)-3(5)-trifluoromethylpyrazoles

Abstract

1-(2-Thienyl)-2-arylazo-4,4,4-trifluorobutane-1,3-diones (4), generated by the condensation of aryldiazonium salts (2) with 4,4,4-trifluoro-1-(2-thienyl)butane-1,3-dione (3), were used as common intermediates to synthesize regioisomeric 4-arylazo-1-phenyl-5(3)-(2-thienyl)-3(5)-trifluoromethylpyrazoles (5 and 6) and 4-arylazo-1-phenyl-3-(2-thienyl)-5-hydroxy-5-trifluoromethylpyrazolines (7) by reacting with phenylhydrazine in neutral conditions. All the synthesized compounds 4, 5, 6 and 7 were screened for their DNA photocleavage activity on pBR322 supercoiled DNA plasmid under UV radiation at λmax 312 nm without any additive. The results indicated that 3-trifluoromethyl isomers (5) photocleaves plasmid DNA better than the corresponding 5-trifluoromethylpyrazoles (6) and 5-hydroxy5-trifluoromethylpyrazolines (7). 4-(4-nitrophenylazo)-1-phenyl-5-(2-thienyl)-3-trifluoromethylpyrazole 5g, exhibited the best potential as DNA photocleaver, cleaving the supercoiled plasmid (Form-I) into smaller fragments at 20 μM of compound with 60 μM of DNA plasmid in DMSO. Selected seventeen compounds were further screened for their cytotoxicity against four cancer cell lines namely MCF-7, BT-474, SBALL and MOLT-4 and again compound 5g was identified as the most potent compound with an IC50 value of 8.6 ± 3.8 μM against MCF-7 cell line.