Genotoxicity of Novel Pyrazolo[4,3-]tetrazolo[1,5-][1,2,4]triazine Sulfonamides in Normal and Cancer Cells In Vitro

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Feb 25

PMID 36835469

Authors

Mateusz Kciuk

Somdutt Mujwar

Beata Marciniak

Adrianna Gielecinska

Karol Bukowski

Mariusz Mojzych

Renata Kontek

Affiliations

Soon will be listed here.

Abstract

Pyrazolo[4,3-]tetrazolo[1,5-][1,2,4]triazine sulfonamides constitute a novel group of heterocyclic compounds with broad biological activities including anticancer properties. The compounds investigated in this study (, , , and ) were found to have antiproliferative activity against BxPC-3 and PC-3 cancer cell lines in micromolar concentrations (IC 0.11-0.33 µM). Here, we studied the genotoxic potential of the tested compounds with alkaline and neutral comet assays, accompanied by immunocytochemical detection of phosphorylated γH2AX. We found that pyrazolo[4,3-]tetrazolo[1,5-][1,2,4]triazine sulfonamides induce significant levels of DNA damage in BxPC-3 and PC-3 cells without causing genotoxic effects in normal human lung fibroblasts (WI-38) when used in their respective IC concentrations (except for ) and showed a dose-dependent increase in DNA damage following 24 h incubation of tested cancer cells with these agents. Furthermore, the influence of compounds on DNA damage response (DDR) factors was assessed using molecular docking and molecular dynamics simulation.

Citing Articles

Pyrazolo[4,3-]tetrazolo[1,5-][1,2,4]triazine Sulfonamides as an Important Scaffold for Anticancer Drug Discovery-In Vitro and In Silico Evaluation.

Kciuk M, Marciniak B, Celik I, Zerroug E, Dubey A, Sundaraj R Int J Mol Sci. 2023; 24(13).

PMID: 37446136 PMC: 10342037. DOI: 10.3390/ijms241310959.

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