Lakshmi Manasa Kesari, Thatikonda Sowjanya, Sigalapalli Dilep Kumar, Sagar Arpita, Kiranmai Gaddam, Kalle Arunasree M, Alvala Mallika, Godugu Chandraiah, Nagesh Narayana, Nagendra Babu Bathini
Department of Fluoro-Agrochemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India.
Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India.
Bioorg Chem. 2020 Aug;101:103983. doi: 10.1016/j.bioorg.2020.103983. Epub 2020 Jun 1.
A series of new β-carboline linked aryl sulfonyl piperazine congeners have been synthesized by coupling various β-carboline acids with substituted aryl sulfonyl piperazines. Evaluation of their anticancer activity against a panel of human cancer cell lines such as colon (HT-29), breast (MDA-MB-231), bone osteosarcoma (MG-63), brain (U87 MG), prostate (PC- 3) and normal monkey kidney (Vero) cell line has been done. Among the series, compound 8ec and 8ed has shown most potent cytotoxicity with an IC values of 2.80 ± 0.10 µM and 0.59 ± 0.28 µM respectively against MG-63 cell line and also potent on other cell lines tested. Compounds 8ec and 8ed was found to inhibit Topo II that is confirmed by specific Topo II inhibition assay. DNA binding studies, cell cycle analysis, Annexin V study indicate that these compounds has potential anticancer activity. Molecular docking studies for compound 8ec and 8ed are incorporated to understand the nature of interaction with topoisomerase IIα and dsDNA.
通过将各种β-咔啉酸与取代的芳基磺酰哌嗪偶联，合成了一系列新型的β-咔啉连接的芳基磺酰哌嗪类似物。已对它们针对一组人类癌细胞系的抗癌活性进行了评估，这些细胞系包括结肠（HT-29）、乳腺（MDA-MB-231）、骨肉瘤（MG-63）、脑（U87 MG）、前列腺（PC-3）以及正常猴肾（Vero）细胞系。在该系列中，化合物8ec和8ed表现出最强的细胞毒性，对MG-63细胞系的IC值分别为2.80±0.10 μM和0.59±0.28 μM，并且对其他测试细胞系也有活性。通过特异性拓扑异构酶II抑制试验证实，化合物8ec和8ed能抑制拓扑异构酶II。DNA结合研究、细胞周期分析、膜联蛋白V研究表明这些化合物具有潜在的抗癌活性。纳入了化合物8ec和8ed的分子对接研究，以了解其与拓扑异构酶IIα和双链DNA相互作用的性质。
