Prodrugs for nitroreductase-based cancer therapy-3: Antitumor activity of the novel dinitroaniline prodrugs/Ssap-NtrB enzyme suicide gene system: Synthesis, in vitro and in silico evaluation in prostate cancer

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dc.authoridTASKIN-TOK, Tugba/0000-0002-0064-8400
dc.authoridGungor, Tugba/0000-0001-5261-1856
dc.authoridAY, Mehmet/0000-0002-1095-1614
dc.authoridComert Onder, Ferah/0000-0002-4037-1979
dc.contributor.authorTokay, Esra
dc.contributor.authorGungor, Tugba
dc.contributor.authorHacioglu, Nelin
dc.contributor.authorOnder, Ferah Cornett
dc.contributor.authorGullhan, Unzile Guven
dc.contributor.authorTok, Tugba Taskin
dc.contributor.authorCelik, Ayhan
dc.date.accessioned2025-01-27T20:24:43Z
dc.date.available2025-01-27T20:24:43Z
dc.date.issued2020
dc.departmentÇanakkale Onsekiz Mart Üniversitesi
dc.description.abstractProdrugs for targeted tumor therapies have been extensively studied in recent years due to not only maximising therapeutic effects on tumor cells but also reducing or eliminating serious side effects on healthy cells. This strategy uses prodrugs which are safe for normal cells and form toxic metabolites (drugs) after selective reduction by enzymes in tumor tissues. In this study, prodrug candidates (1-36) containing nitro were designed, synthesized and characterized within the scope of chemical experiments. Drug-likeness properties of prodrug candidates were analyzed using DS 2018 to investigate undesired toxicity effects. In vitro cytotoxic effects of prodrug canditates were performed with MTT assay for human hepatoma cells (Hep3B) and prostate cancer cells (PC3) and human umbilical vein endothelial cells (HUVEC) as healthy control. Non-toxic compounds (3, 5, 7,10, 12, 15,17, 19 and 21-23), and also compounds (1, 2, 5, 6, 9, 11, 14, 16, 20 and 24) which had low toxic effects, were selected to examine their suitability as prodrug canditates. The reduction profiles and kinetic studies of prodrug/Ssap-NtrB combinations were performed with biochemical analyses. Then, selected prodrug/Ssap-NtrB combinations were applied to prostate cancer cells to determine toxicity. The results of theoretical, in vitro cytotoxic and biochemical studies suggest 14/Ssap-NtrB, 22/Ssap-NtrB and 24/Ssap-NtrB may be potential prodrug/enzyme combinations for nitroreductase (Ntr)-based prostate cancer therapy. (C) 2019 Elsevier Masson SAS. All rights reserved.
dc.description.sponsorshipScientific and Technological Research Council of Turkey-TUBITAK [110T754, 113Z706]
dc.description.sponsorshipThis study was financially supported by a research grant from Scientific and Technological Research Council of Turkey-TUBITAK (Grant No. 110T754 and 113Z706). The numerical calculations reported in this abstract were all performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources).
dc.identifier.doi10.1016/j.ejmech.2019.111937
dc.identifier.issn0223-5234
dc.identifier.issn1768-3254
dc.identifier.pmid31841727
dc.identifier.scopus2-s2.0-85076241209
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.ejmech.2019.111937
dc.identifier.urihttps://hdl.handle.net/20.500.12428/22323
dc.identifier.volume187
dc.identifier.wosWOS:000510525000026
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier France-Editions Scientifiques Medicales Elsevier
dc.relation.ispartofEuropean Journal of Medicinal Chemistry
dc.relation.publicationcategoryinfo:eu-repo/semantics/openAccess
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WoS_20250125
dc.subjectDinitroaniline
dc.subjectProdrug
dc.subjectSsap-NtrB
dc.subjectNitroreductase
dc.subjectEnzymatic activity
dc.subjectCytotoxicity
dc.subjectProstate cancer
dc.subjectIn silica studies
dc.titleProdrugs for nitroreductase-based cancer therapy-3: Antitumor activity of the novel dinitroaniline prodrugs/Ssap-NtrB enzyme suicide gene system: Synthesis, in vitro and in silico evaluation in prostate cancer
dc.typeArticle

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