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首页> 外文期刊>RSC Advances >Synthesis and biological evaluation of new 2,5-dimethylthiophene/furan based N-acetyl pyrazolines as selective topoisomerase II inhibitors
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Synthesis and biological evaluation of new 2,5-dimethylthiophene/furan based N-acetyl pyrazolines as selective topoisomerase II inhibitors

机译：新型2,5-二甲基噻吩/呋喃的N-乙酰吡唑啉的合成与生物学评价为选择性拓扑异构酶II抑制剂

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摘要

Based on reported pharmacophores as topoisomerase inhibitors, 2,5-dimethylthiophene/furan based N -acetyl pyrazolines were designed and envisaged as topoisomerase inhibitors. The target compounds were synthesized and tested in vitro against human topoisomerases in decatenation, relaxation, cleavage complex and DNA intercalation assays. Out of 29 compounds, three ( 10 , 11 and 29 ) showed potent and selective topoisomerase II inhibitory activity with no intercalation with DNA. Further, molecular docking studies also endorsed them as ATP dependent topoisomerase II catalytic inhibitors. These compounds exerted potential anticancer effects on breast, colon, lung and prostate cancer cell lines at a low micromolar level, as compared to etoposide, and low toxicity to normal cells. Apart from the topoisomerase II inhibition, these compounds also induced a reactive oxygen species (ROS) level in cancer cells. The cell cycle analyses showed their apoptotic effect at the G1 phase.
机译：基于报告的药物团作为拓扑异构酶抑制剂，设计了和设想了2,5-二甲基噻吩/呋喃的基乙酰吡唑啉，作为拓扑异构酶抑制剂。在解体，弛豫，切割复合物和DNA插层和DNA插层测定中，在体外合成并测试靶化合物并在体外测试。在29个化合物中，三（10,11和29）显示有效和选择性的拓扑异构酶II抑制活性，没有与DNA嵌入的抑制活性。此外，作为ATP依赖性拓扑异构酶II催化抑制剂，分子对接研究也将它们归纳。与依托泊苷相比，这些化合物对低微摩拉水平的潜在抗癌对乳腺，结肠，肺和前列腺癌细胞系产生潜在的抗癌影响，与依托泊苷和对正常细胞的低毒性相比。除了拓扑异构酶II抑制外，这些化合物还诱导癌细胞中的反应性氧物质（ROS）水平。细胞循环分析显示它们在G1相处的凋亡效应。

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