{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:21Z","timestamp":1787028501078,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pyrazolo[4,3-e]tetrazolo[1,5-b][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 (MM134, -6, -7, and 9) were found to have antiproliferative activity against BxPC-3 and PC-3 cancer cell lines in micromolar concentrations (IC50 0.11\u20130.33 \u00b5M). Here, we studied the genotoxic potential of the tested compounds with alkaline and neutral comet assays, accompanied by immunocytochemical detection of phosphorylated \u03b3H2AX. We found that pyrazolo[4,3-e]tetrazolo[1,5-b][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 IC50 concentrations (except for MM134) and showed a dose-dependent increase in DNA damage following 24 h incubation of tested cancer cells with these agents. Furthermore, the influence of MM compounds on DNA damage response (DDR) factors was assessed using molecular docking and molecular dynamics simulation.<\/jats:p>","DOI":"10.3390\/ijms24044053","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T03:53:49Z","timestamp":1676606029000},"page":"4053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Genotoxicity of Novel Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides in Normal and Cancer Cells In Vitro"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8616-3825","authenticated-orcid":false,"given":"Mateusz","family":"Kciuk","sequence":"first","affiliation":[{"name":"Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha 12\/16, 90-237 Lodz, Poland"},{"name":"Doctoral School of Exact and Natural Sciences, University of Lodz, Banacha Street 12\/16, 90-237 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4037-5475","authenticated-orcid":false,"given":"Somdutt","family":"Mujwar","sequence":"additional","affiliation":[{"name":"Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8109-6478","authenticated-orcid":false,"given":"Beata","family":"Marciniak","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha 12\/16, 90-237 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9562-3582","authenticated-orcid":false,"given":"Adrianna","family":"Gieleci\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha 12\/16, 90-237 Lodz, Poland"},{"name":"Doctoral School of Exact and Natural Sciences, University of Lodz, Banacha Street 12\/16, 90-237 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2517-9898","authenticated-orcid":false,"given":"Karol","family":"Bukowski","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha 12\/16, 90-237 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9884-6068","authenticated-orcid":false,"given":"Mariusz","family":"Mojzych","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Siedlce University of Natural Sciences and Humanities, 3 Maja 54, 08-110 Siedlce, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2859-9839","authenticated-orcid":false,"given":"Renata","family":"Kontek","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha 12\/16, 90-237 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.18632\/oncoscience.423","article-title":"Combating resistance to DNA damaging agents","volume":"5","author":"Choi","year":"2018","journal-title":"Oncoscience"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mukhtar, M., Bilal, M., Rahdar, A., Barani, M., Arshad, R., Behl, T., Brisc, C., Banica, F., and Bungau, S. 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