基于潜在氨基酸的喹唑啉酮类似物的抗癌和 DNA 结合研究：合成、SAR 和分子对接。
Anticancer and DNA binding studies of potential amino acids based quinazolinone analogs: Synthesis, SAR and molecular docking.
机构信息
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, Karnataka, India.
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, Karnataka, India.
出版信息
Bioorg Chem. 2019 Jun;87:252-264. doi: 10.1016/j.bioorg.2019.03.038. Epub 2019 Mar 19.
A novel series of amino acids conjugated quinazolinone-Schiff's bases were synthesized and screened for their in vitro anticancer activity and validated by molecular docking and DNA binding studies. In the present investigations, compounds 32, 33, 34, 41, 42 and 43 showed most potent anticancer activity against tested cancer cell lines and DNA binding study using methyl green comparing to doxorubicin and ethidium bromide as a positive control respectively. The structure-activity relationship (SAR) revealed that the tryptophan and phenylalanine derived electron donating groups (OH and OCH) favored DNA binding studies and anticancer activity whereas; electron withdrawing groups (Cl, NO, and F) showed least anticancer activity. The molecular docking study, binding interactions of the most active compounds 33, 34, 42 and 43 stacked with A-T rich regions of the DNA minor groove by surface binding interactions were confirmed.
合成了一系列新型氨基酸偶联喹唑啉酮-Schiff 碱，并对其进行了体外抗癌活性筛选，通过分子对接和 DNA 结合研究进行了验证。在本研究中，化合物 32、33、34、41、42 和 43 对测试的癌细胞系表现出最强的抗癌活性，与阿霉素和溴化乙锭作为阳性对照相比，使用甲基绿进行的 DNA 结合研究。构效关系（SAR）表明，色氨酸和苯丙氨酸衍生的供电子基团（OH 和 OCH）有利于 DNA 结合研究和抗癌活性，而吸电子基团（Cl、NO 和 F）则表现出最低的抗癌活性。分子对接研究证实，最活性化合物 33、34、42 和 43 与 DNA 小沟中富含 A-T 的区域通过表面结合相互作用堆积。
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