4β-amidotriazole linked podophyllotoxin congeners: DNA topoisomerase-IIα inhibition and potential anticancer agents for prostate cancer

Reddy, V, Bonam, S, Telukutla, S, Akunuri, R, Naidu, V, Nayak, V, Bhargava, S, Kumar, H, Srihari, P and Kamal, A 2018, '4β-amidotriazole linked podophyllotoxin congeners: DNA topoisomerase-IIα inhibition and potential anticancer agents for prostate cancer', European Journal of Medicinal Chemistry, vol. 144, pp. 595-611.


Document type: Journal Article
Collection: Journal Articles

Title 4β-amidotriazole linked podophyllotoxin congeners: DNA topoisomerase-IIα inhibition and potential anticancer agents for prostate cancer
Author(s) Reddy, V
Bonam, S
Telukutla, S
Akunuri, R
Naidu, V
Nayak, V
Bhargava, S
Kumar, H
Srihari, P
Kamal, A
Year 2018
Journal name European Journal of Medicinal Chemistry
Volume number 144
Start page 595
End page 611
Total pages 17
Publisher Elsevier Masson
Abstract Topoisomerases (topo-I and topo-II) have occupied a significant role in DNA replication, transcription, and are a promising set of antitumor targets. In the present approach, a series of new 4 beta-amidotriazole linked podophyllotoxin derivatives (10a-i and 11a-k) were designed, synthesized by employing the click chemistry and their biological activities were evaluated. The majority of derivatives showed promising antiproliferative activity with IC50 values ranging from 1 to 10 mu M on the six human cancer cell lines; cervical (HeLa), breast (MCF-7), prostate (DU-145), lung (A549), liver (HepG2) and colon (HT-29). Among them, some of the congeners 10b, 10g and 10i have shown remarkable cytotoxicity with IC50 values of, < 1 mu M against the tested cancer cell lines and found to be more active than etoposide. Topoisomerase-mediated DNA relaxation assay results showed that the derivatives could efficiently inhibit the activity of topoisomerase-II. In addition, flow cytometry analysis on DU-145 cells revealed that these compounds arrest G2/M phase of cell cycle. Further apoptotic studies were also performed on these DU-145 cells, which showed that this class of compounds could induce apoptosis effectively
Subject Medicinal and Biomolecular Chemistry not elsewhere classified
Keyword(s) Anticancer activity
Apoptosis
Cell cycle
Topo-II inhibition
Triazole
DOI - identifier 10.1016/j.ejmech.2017.12.050
Copyright notice © 2017 Elsevier Masson SAS. All rights reserved.
ISSN 0223-5234
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