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

Authors :: Sathish M
Kavitha B
Nayak VL
Tangella Y
Ajitha A
Nekkanti S
Alarifi A
Shankaraiah N
Nagesh N
Kamal A
Source :: European journal of medicinal chemistry [Eur J Med Chem] 2018 Jan 20; Vol. 144, pp. 557-571. Date of Electronic Publication: 2017 Dec 16.
Publication Year :: 2018
Abstract: A series of new podophyllotoxin linked β-carboline congeners have been synthesized by coupling various substituted β-carboline acids with 4β-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 IC <subscript>50</subscript> values of 1.07 ± 0.07 μM 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.<br /> (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Subjects :: Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Carbolines chemistry
Cell Line, Tumor
Cell Proliferation drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Molecular Docking Simulation
Molecular Structure
Podophyllotoxin chemistry
Structure-Activity Relationship
Topoisomerase II Inhibitors chemical synthesis
Topoisomerase II Inhibitors chemistry
Antineoplastic Agents pharmacology
Carbolines pharmacology
DNA Topoisomerases, Type II metabolism
Podophyllotoxin pharmacology
Topoisomerase II Inhibitors pharmacology

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