Synthesis of podophyllotoxin linked β-carboline congeners as potential anticancer agents and DNA topoisomerase II inhibitors

被引：73

作者：

Sathish, Manda ^{[1
]}

Kavitha, Botla ^{[2
]}

Nayak, V. Lakshma ^{[1
]}

Tangella, Yellaiah ^{[1
]}

Ajitha, Ayyappan ^{[3
]}

Nekkanti, Shalini ^{[2
]}

Alarifi, Abdullah ^{[4
]}

Shankaraiah, Nagula ^{[2
]}

Nagesh, Narayana ^{[3
]}

Kamal, Ahmed ^{[1
,2
,5
]}

机构：

[1] CSIR, Indian Inst Chem Technol, Med Chem & Pharmacol, Hyderabad 500007, Andhra Pradesh, India

[2] NIPER, Dept Med Chem, Hyderabad 500037, Andhra Pradesh, India

[3] CSIR, Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India

[4] King Saud Univ, Coll Sci, Chem Dept, Catalyt Chem Res Chair, Riyadh 11451, Saudi Arabia

[5] Jamia Hamdad Univ, SPER, New Delhi 110062, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 144卷

关键词：

beta-Carbolines; Podophyllotoxin; Topoisomerase II inhibition; Cytotoxicity; Docking; CYCLIN-DEPENDENT KINASES; CANCER-CHEMOTHERAPY; BIOLOGICAL EVALUATION; ANTITUMOR AGENTS; DERIVATIVES; BINDING; DESIGN; ETOPOSIDE; APOPTOSIS; ANALOGS;

D O I：

10.1016/j.ejmech.2017.12.055

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of new podophyllotoxin linked beta-carboline congeners have been synthesized by coupling various substituted beta-carboline acids with 4 beta-aminopodophyllotoxin. Evaluation of their anticancer activity against a panel of human cancer cell lines such as lung cancer (A549), prostate cancer (DU-145), MDA MB-231 (breast cancer), HT-29 (colon cancer) and HeLa (cervical cancer) suggested that 7i and 7j are the most cytotoxic compounds with IC50 values of 1.07 +/- 0.07 mu M and 1.14 +/- 0.16 respectively against DU-145 cell line. Further, detailed biological studies such as cell cycle analysis, topoisomerase II inhibition, Comet assay, DNA binding studies and docking studies have revealed that these congeners are DNA interacting topoisomerase II inhibitors. (C) 2017 Elsevier Masson SAS. All rights reserved.

引用

页码：557 / 571

页数：15

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