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新型基于邻苯二甲酰亚胺的衍生物作为有效的抗癌药物对拓扑异构酶 II 的抑制和 DNA 嵌入作用：设计、合成、抗增殖、对接和研究。

Topo II inhibition and DNA intercalation by new phthalazine-based derivatives as potent anticancer agents: design, synthesis, anti-proliferative, docking, and studies.

机构信息

Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt.

Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, Egypt.

出版信息

J Enzyme Inhib Med Chem. 2022 Dec;37(1):299-314. doi: 10.1080/14756366.2021.2007905.

DOI:10.1080/14756366.2021.2007905
PMID:34894955
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8667898/
Abstract

This research presents the design and synthesis of a novel series of phthalazine derivatives as Topo II inhibitors, DNA intercalators, and cytotoxic agents. testing of the new compounds against HepG-2, MCF-7, and HCT-116 cell lines confirmed their potent cytotoxic activity with low IC values. Topo II inhibition and DNA intercalating activities were evaluated for the most cytotoxic members. IC values determination demonstrated Topo II inhibitory activities and DNA intercalating affinities of the tested compounds at a micromolar level. Amongst, compound was the most potent member. It inhibited Topo II enzyme at IC value of 7.02 ± 0.54 µM with DNA intercalating IC of 26.19 ± 1.14 µM. Compound was then subjected to an antitumor examination. It inhibited tumour proliferation reducing solid tumour volume and mass. Additionally, it restored liver enzymes, proteins, and CBC parameters near-normal, indicating a remarkable amelioration in their functions along with histopathological examinations.

摘要

本研究设计并合成了一系列新型的酞嗪衍生物，作为拓扑异构酶 II 抑制剂、DNA 嵌入剂和细胞毒性剂。对新化合物进行的 HepG-2、MCF-7 和 HCT-116 细胞系的测试证实了它们具有低 IC 值的强大细胞毒性活性。对最具细胞毒性的成员进行了拓扑异构酶 II 抑制和 DNA 嵌入活性测试。IC 值测定表明，所测试化合物在微摩尔水平上具有拓扑异构酶 II 抑制活性和 DNA 嵌入亲和力。其中，化合物 是最有效的成员。它在 IC 值为 7.02 ± 0.54 μM 时抑制拓扑异构酶 II 酶，在 IC 值为 26.19 ± 1.14 μM 时具有 DNA 嵌入活性。然后对化合物 进行了抗肿瘤检查。它抑制肿瘤增殖，减少实体瘤体积和质量。此外，它还恢复了肝脏酶、蛋白质和 CBC 参数接近正常，表明其功能得到了显著改善，同时还进行了组织病理学检查。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42cd/8667898/21cd1962dd06/IENZ_A_2007905_F0011_C.jpg
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