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新型3-取代碘化4-(3)-喹唑啉酮的合成、抗肿瘤活性、3D-QSAR及分子对接研究

Synthesis, antitumor activity, 3D-QSAR and molecular docking studies of new iodinated 4-(3)-quinazolinones 3-substituted.

作者信息

Pérez-Fehrmann Marcia, Kesternich Víctor, Puelles Arturo, Quezada Víctor, Salazar Fernanda, Christen Philippe, Castillo Jonathan, Cárcamo Juan Guillermo, Castro-Alvarez Alejandro, Nelson Ronald

机构信息

Departamento de Química, Facultad de Ciencias, Universidad Católica del Norte Av. Angamos 0610 Antofagasta 1270709 Chile

School of Pharmaceutical Sciences University of Geneva 1211 Geneva 4 Switzerland.

出版信息

RSC Adv. 2022 Aug 2;12(33):21340-21352. doi: 10.1039/d2ra03684c. eCollection 2022 Jul 21.

DOI:10.1039/d2ra03684c
PMID:35975048
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9344282/
Abstract

A novel series of 6-iodo-2-methylquinazolin-4-(3)-one derivatives, 3a-n, were synthesized and evaluated for their cytotoxic activity. Compounds 3a, 3b, 3d, 3e, and 3h showed remarkable cytotoxic activity on specific human cancer cell lines when compared to the anti-cancer drug, paclitaxel. Compound 3a was found to be particularly effective on promyelocytic leukaemia HL60 and non-Hodgkin lymphoma U937, with IC values of 21 and 30 μM, respectively. Compound 3d showed significant activity against cervical cancer HeLa (IC = 10 μM). The compounds 3e and 3h were strongly active against glioblastoma multiform tumour T98G, with IC values of 12 and 22 μM, respectively. These five compounds showed an interesting cytotoxic activity on four human cancer cell types of high incidence. The molecular docking results reveal a good correlation between experimental activity and calculated binding affinity on dihydrofolate reductase (DHFR). Docking studies proved 3d as the most potent compound. In addition, the three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis exhibited activities that may indicate the existence of electron-withdrawing and lipophilic groups at the -position of the phenyl ring and hydrophobic interactions of the quinazolinic ring in the DHFR active site.

摘要

合成了一系列新型的6-碘-2-甲基喹唑啉-4（3H）-酮衍生物3a-n，并对其细胞毒性活性进行了评估。与抗癌药物紫杉醇相比，化合物3a、3b、3d、3e和3h对特定的人类癌细胞系表现出显著的细胞毒性活性。发现化合物3a对早幼粒细胞白血病HL60和非霍奇金淋巴瘤U937特别有效，IC值分别为21和30μM。化合物3d对宫颈癌HeLa显示出显著活性（IC = 10μM）。化合物3e和3h对多形性胶质母细胞瘤T98G具有强烈活性，IC值分别为12和22μM。这五种化合物对四种高发性人类癌细胞类型表现出有趣的细胞毒性活性。分子对接结果揭示了实验活性与二氢叶酸还原酶（DHFR）上计算的结合亲和力之间的良好相关性。对接研究证明3d是最有效的化合物。此外，三维定量构效关系（3D-QSAR）分析显示的活性可能表明在苯环的β位存在吸电子和亲脂性基团，以及喹唑啉环在DHFR活性位点的疏水相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04bf/9344282/0909e4c624df/d2ra03684c-f8.jpg
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2
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J Enzyme Inhib Med Chem. 2022 Dec;37(1):686-700. doi: 10.1080/14756366.2022.2036985.
3
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Chem Biodivers. 2021 Dec;18(12):e2100687. doi: 10.1002/cbdv.202100687. Epub 2021 Nov 16.
4
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J Org Chem. 2021 Nov 5;86(21):14695-14704. doi: 10.1021/acs.joc.1c01510. Epub 2021 Sep 27.
5
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6
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