作为一氧化氮供体的选择性 COX-2、芳香化酶、B-RAFV600E 和表皮生长因子受体抑制剂塞来昔布类似物：设计、合成、抗炎/抗增殖活性、细胞凋亡和分子模型研究

IF 5.6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2023-12-01 DOI:10.1080/14756366.2023.2290461

Wael A. A. Fadaly, M. T. Nemr, Taha H. Zidan, Fatma E. A. Mohamed, Marwa M. Abdelhakeem, Nour N. Abu Jayab, Hany A. Omar, Khaled R. A. Abdellatif

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引用次数: 0

摘要

摘要:合成了一系列具有抗炎和抗癌活性的双三唑19a- 1杂交分子，并对其细胞周期阻滞和NO释放进行了评价。化合物19c、19f、19h、19l对COX-2的选择性指数为18.48 ~ 49.38(塞来昔布为21.10)，抑制MCF-7的IC50为9 ~ 16 μM(他莫昔芬为27.9 μM)。与索拉非尼(IC50 = 3.5 μM)相比，对HEP-3B具有良好的抑制活性，IC50 = 4.5 ~ 14 μM。衍生物19e、19j、19k、19l对HCT-116的抑制作用IC50为5.3 ~ 13.7 μM，而5-FU对HCT-116的抑制作用IC50为4.8 μM。化合物19c、19f、19h、19l对A549具有较好的抑制活性，IC50为3 ~ 4.5 μM，而5-FU对A549的IC50为6 μM。化合物19c、19f、19h、19l分别抑制芳香化酶(IC50分别为22.40、23.20、22.70、30.30 μM)、EGFR (IC50分别为0.112、0.205、0.169和0.066 μM)和B-RAFV600E (IC50分别为0.09、0.06、0.07和0.05 μM)。

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New 1,2,3-triazole/1,2,4-triazole hybrids linked to oxime moiety as nitric oxide donor selective COX-2, aromatase, B-RAFV600E and EGFR inhibitors celecoxib analogs: design, synthesis, anti-inflammatory/anti-proliferative activities, apoptosis and molecular modeling study

Abstract A new series of bis-triazole 19a-l was synthesised for the purpose of being hybrid molecules with both anti-inflammatory and anti-cancer activities and assessed for cell cycle arrest, NO release. Compounds 19c, 19f, 19h, 19 l exhibited COX-2 selectivity indexes in the range of 18.48 to 49.38 compared to celecoxib S.I. = 21.10), inhibit MCF-7 with IC50 = 9–16 μM compared to tamoxifen (IC50 = 27.9 μM). and showed good inhibitory activity against HEP-3B with IC50 = 4.5–14 μM compared to sorafenib (IC50 = 3.5 μM) (HEP-3B). Moreover, derivatives 19e, 19j, 19k, 19 l inhibit HCT-116 with IC50 = 5.3–13.7 μM compared to 5-FU with IC50 = 4.8 μM (HCT-116). Compounds 19c, 19f, 19h, 19 l showed excellent inhibitory activity against A549 with IC50 = 3–4.5 μM compared to 5-FU with IC50 = 6 μM (A549). Compounds 19c, 19f, 19h, 19 l inhibit aromatase (IC50 of 22.40, 23.20, 22.70, 30.30 μM), EGFR (IC50 of 0.112, 0.205, 0.169 and 0.066 μM) and B-RAFV600E (IC50 of 0.09, 0.06, 0.07 and 0.05 μM).

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来源期刊

Journal of Enzyme Inhibition and Medicinal Chemistry 医学-生化与分子生物学

CiteScore

10.30

自引率

10.70%

发文量

195

审稿时长

4-8 weeks

期刊介绍： Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.