Indrasena Reddy K, Aruna C, Manisha M, Srihari K, Sudhakar Babu K, Vijayakumar V, Sarveswari S, Priya R, Amrita A, Siva R
Department of Chemistry, Sri Krishnadevaraya University, Anantapur 515055, India.
DBT-HTS, Piramal Entreprises Limited, Nirlon Complex, Goregaon East, Mumbai 400063, India.
J Photochem Photobiol B. 2017 Mar;168:89-97. doi: 10.1016/j.jphotobiol.2017.02.003. Epub 2017 Feb 7.
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, H NMR, 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-1H-pyrazol-1-yl)-1H-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-2H-pyrrol-2-yl)-1H-pyrazol-5-yl)benzamide and 2,6-difluoro-N-(3-isopropoxy-1-isopropyl-4-(3,5-dimethyl-2H-pyrrol-2-yl)-1H-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.
采用连续法从3,5-二甲基吡唑合成了一系列新的双吡唑6a-t。所有这些化合物均通过红外光谱、氢核磁共振、碳核磁共振和质谱数据进行了表征。通过分子对接和吸收光谱技术研究了新合成的双吡唑与DNA的相互作用。在所有双吡唑化合物中，通过计算机分析发现6h化合物具有较低的构象能量。通过紫外-可见光谱研究考察了该系列6a-t中每个分子与不同浓度DNA的相互作用。对化合物6a、6b、6g、6h、6d、6i、6k、6n、6s与DNA特异性结合的紫外-可见光谱研究显示了光谱位移，并对结果进行了讨论。此外，对化合物6a-t进行了针对人胰腺腺癌、人非小细胞肺癌细胞系的体外细胞毒性研究。在筛选出的化合物中，N-(3-异丙氧基-1-异丙基-4-(3,5-二甲基-1H-吡唑-1-基)-1H-吡唑-5-基)环丁烷甲酰胺和N-(5'-异丙氧基-2'-异丙基-3,5-二甲基-2'H-[1,4']联吡唑基-3'-基)-二甲烷磺酰胺被发现为先导分子，因为它们对本研究中使用的两种癌细胞系均表现出有前景的活性，而化合物4-(三氟甲基)-N-(3-异丙氧基-1-异丙基-4-(3,5-二甲基-2H-吡咯-2-基)-1H-吡唑-5-基)苯甲酰胺和2,6-二氟-N-(3-异丙氧基-1-异丙基-4-(3,5-二甲基-2H-吡咯-2-基)-1H-吡唑-5-基)苯甲酰胺仅对胰腺细胞系有活性。其余所有化合物对两种细胞系均表现出中度至良好的活性。
