Kumar Vinod, Kaur Kamalneet, Karelia Deepkamal N, Beniwal Vikas, Gupta Girish Kumar, Sharma Arun K, Gupta Akhilesh Kumar
Department of Chemistry, M. M. University, Mullana-Ambala 133207, India.
Department of Chemistry, M. M. University, Mullana-Ambala 133207, India.
Eur J Med Chem. 2014 Jun 23;81:267-76. doi: 10.1016/j.ejmech.2014.05.004. Epub 2014 May 6.
In continuation of our efforts to find new biologically active agents, regioselective synthesis of a series of 2-(3,5-dimethyl-1H-pyrazol-1-yl)-1-arylethanones 4a-k has been achieved under facile, extremely mild and greener reaction conditions with excellent yields. Moreover, one pot multicomponent reaction has also been reinvestigated under previously reported solvent conditions to prepare 4a-b and found that the reaction generates significant amount of side products. The chemical structures of 4a-k were established on the basis of a combined use of IR, NMR ((1)H, (13)C) spectroscopy, mass spectrometry and elemental analysis. All the compounds were evaluated for their antibacterial, DNA photocleavage and anticancer activities. Among all, 2-(3,5-dimethyl-1H-pyrazol-1-yl)-1-(naphth-2-yl)ethanone 4j displayed good inhibitory profile against Escherichia coli and Staphylococcus aureus which was about 50% and 25% of the Ampicillin (standard drug), respectively. The compounds, 4a and 4f showed relatively moderate inhibition against Psuedomonas aeruginosa and E. coli. In DNA photocleavage study, compounds 4c and 4d were found to be highly active and completely degraded both forms of DNA (SC and OC), even at a very low concentration of 1 μg (4c) under irradiation of UV light. However, 4h and 4f resulted in complete DNA degradation at 30 μg concentration. Moreover, 4h showed fluorescence at 15 μg concentration and increased the intensity of both bands of DNA (SC and OC) as compared to control. On the other hand, to valorize the biological potential, the compounds were screened for their cytotoxic activity on colon (HCT116 and HT29), prostate (DU145), ovarian (SKOV3) and lung (A549) cancer cell lines. The compound 4j was found to be cytotoxic to all the cancer cell lines, except SKOV3, with more selectivity towards the colon cancer cell lines (HCT116, HT29) and A549 lung cancer cell line. On A549 lung cancer cell line, 4j and 4k exhibited similar potency as carboplatin in inhibiting cell viability.
为持续寻找新的生物活性剂，我们在简便、极其温和且更环保的反应条件下，以优异产率实现了一系列2-(3,5-二甲基-1H-吡唑-1-基)-1-芳基乙酮4a - k的区域选择性合成。此外，还在先前报道的溶剂条件下重新研究了一锅多组分反应以制备4a - b，结果发现该反应产生大量副产物。4a - k的化学结构通过红外光谱、核磁共振((1)H、(13)C)光谱、质谱和元素分析联用得以确定。对所有化合物进行了抗菌、DNA光裂解和抗癌活性评估。其中，2-(3,5-二甲基-1H-吡唑-1-基)-1-(萘-2-基)乙酮4j对大肠杆菌和金黄色葡萄球菌显示出良好的抑制作用，分别约为氨苄西林（标准药物）的50%和25%。化合物4a和4f对铜绿假单胞菌和大肠杆菌表现出相对中等程度的抑制。在DNA光裂解研究中，发现化合物4c和4d具有高活性，即使在紫外线照射下浓度低至1 μg（4c）时，也能完全降解两种形式的DNA（超螺旋和开环）。然而，4h和4f在30 μg浓度时导致DNA完全降解。此外，4h在15 μg浓度时显示出荧光，并且与对照相比增加了DNA两条带（超螺旋和开环）的强度。另一方面，为评估其生物潜力，对这些化合物在结肠（HCT116和HT29）、前列腺（DU145）、卵巢（SKOV3）和肺癌（A549）细胞系上进行了细胞毒性活性筛选。发现化合物4j对除SKOV3外的所有癌细胞系均具有细胞毒性，对结肠癌细胞系（HCT116、HT29）和A549肺癌细胞系具有更高的选择性。在A549肺癌细胞系上，4j和4k在抑制细胞活力方面表现出与卡铂相似的效力。
