Design and synthesis of some -carboline derivatives as multi-target anticancer agents

被引：31

作者：

Abdelsalam, Mohamed A. ^{[1
]}

AboulWafa, Omaima M. ^{[1
]}

Badawey, El-Sayed A. M. ^{[1
]}

El-Shoukrofy, Mai S. ^{[1
]}

El-Miligy, Mostafa M. ^{[1
]}

Gouda, Noha ^{[2
]}

机构：

[1] Univ Alexandria, Dept Pharmaceut Chem, Fac Pharm, Alexandria 21521, Egypt

[2] Univ Alexandria, Dept Pharmaceut, Fac Pharm, Alexandria 21521, Egypt

来源：

FUTURE MEDICINAL CHEMISTRY | 2018年 / 10卷 / 24期

关键词：

anticancer activity; apoptosis; -carboline; cell cycle arrest; docking; KSP; multitarget agents; National Cancer Institute; topoisomerase-I; triazoles; BIOLOGICAL EVALUATION; TOPOISOMERASE-II; DRUG DISCOVERY; DNA; ANTITUMOR; CANCER; INHIBITORS; CHROMATOGRAPHY; LIPOPHILICITY; CAMPTOTHECIN;

D O I：

10.4155/fmc-2018-0226

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Aim: Some anticancer -carbolines exhibited dual inhibition of topo-I and KSP. Methodology/Results: Novel -carbolines were synthesized and screened for their anticancer activity according to the NCI protocol. Five dose assays results indicated that compounds 9, 10, 12, 17 and 20 were potent and non selective anticancer agents; the sulfanyltriazole 12 was the most potent. Compounds 10, 12 and 20 showed dual topo-I and KSP inhibition with compound 12 being the most potent. Active compounds elicited Pre-G1 apoptosis and cell cycle arrest at G2/M phase of melanoma MDA-MB-435 cells. Docking results, in silico physicochemical and absorption, distribution, metabolism, excretion (ADME) properties were appropriate. Conclusion: Compounds 10, 12 and 20 are potent apoptosis-inducing multitarget anticancer agents that act via dual inhibition of topo-I and KSP-ATPase.

引用

页码：2791 / 2814

页数：24

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