Synthesis, DNA binding and in-vitro cytotoxicity studies on novel bis-pyrazoles

Abstract A new series of bis-pyrazoles 6a - t were synthesized from 3,5-dimethyl pyrazole using sequential approach. All these compounds were characterized by IR, 1 H NMR, 13 C NMR and mass spectral data. The interaction of newly synthesized bis-pyrazoles with DNA was investigated through molecular docking and absorption spectroscopic technique. Among all bis-pyrazoles compounds, the 6h compound showed lower conformational energy through in silico analysis. The interaction of each molecule in this series 6a - t with the various concentrations of DNA was examined through the UV–visible spectroscopic studies. The UV–visible spectroscopy studies on the specific binding of compound 6a , 6b , 6g , 6h , 6d , 6i , 6k , 6n , 6s with DNA have exhibited spectral shifts and the results were discussed. In further the compounds 6a - t were subjected to the in-vitro cytotoxicity studies against human pancreatic adenocarcinoma, human non-small cell lung carcinoma cell lines. Among the screened compounds, N -(3-isopropoxy-1-isopropyl-4-(3,5-dimethyl-1 H -pyrazol-1-yl)-1 H -pyrazol-5-yl)cyclobutane carboxamide and N -(5′-Isopropoxy-2′-isopropyl-3,5-dimethyl-2′ H -[1,4′] bipyrazolyl-3′-yl)-dimethane sulfonamide were found as lead molecules since they have exhibited promising activity against both the cancer cell lines used in this study, whereas the compounds 4-(trifluoromethyl)- N -(3-isopropoxy-1-isopropyl-4-(3,5-dimethyl-2 H -pyrrol-2-yl)-1 H -pyrazol-5-yl)benzamide and 2,6-difluoro- N -(3-isopropoxy-1-isopropyl-4-(3,5-dimethyl-2 H -pyrrol-2-yl)-1 H -pyrazol-5-yl) benzamide were found to be active against the pancreatic cell line only. Rest all the other compounds were found to exhibit moderate to good activity towards both the cell lines.