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
dc.authorid | TASKIN-TOK, Tugba/0000-0002-0064-8400 | |
dc.authorid | Gungor, Tugba/0000-0001-5261-1856 | |
dc.authorid | AY, Mehmet/0000-0002-1095-1614 | |
dc.authorid | Comert Onder, Ferah/0000-0002-4037-1979 | |
dc.contributor.author | Tokay, Esra | |
dc.contributor.author | Gungor, Tugba | |
dc.contributor.author | Hacioglu, Nelin | |
dc.contributor.author | Onder, Ferah Cornett | |
dc.contributor.author | Gullhan, Unzile Guven | |
dc.contributor.author | Tok, Tugba Taskin | |
dc.contributor.author | Celik, Ayhan | |
dc.date.accessioned | 2025-01-27T20:24:43Z | |
dc.date.available | 2025-01-27T20:24:43Z | |
dc.date.issued | 2020 | |
dc.department | Çanakkale Onsekiz Mart Üniversitesi | |
dc.description.abstract | Prodrugs 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.sponsorship | Scientific and Technological Research Council of Turkey-TUBITAK [110T754, 113Z706] | |
dc.description.sponsorship | This 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.doi | 10.1016/j.ejmech.2019.111937 | |
dc.identifier.issn | 0223-5234 | |
dc.identifier.issn | 1768-3254 | |
dc.identifier.pmid | 31841727 | |
dc.identifier.scopus | 2-s2.0-85076241209 | |
dc.identifier.scopusquality | Q1 | |
dc.identifier.uri | https://doi.org/10.1016/j.ejmech.2019.111937 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12428/22323 | |
dc.identifier.volume | 187 | |
dc.identifier.wos | WOS:000510525000026 | |
dc.identifier.wosquality | Q1 | |
dc.indekslendigikaynak | Web of Science | |
dc.indekslendigikaynak | Scopus | |
dc.indekslendigikaynak | PubMed | |
dc.language.iso | en | |
dc.publisher | Elsevier France-Editions Scientifiques Medicales Elsevier | |
dc.relation.ispartof | European Journal of Medicinal Chemistry | |
dc.relation.publicationcategory | info:eu-repo/semantics/openAccess | |
dc.rights | info:eu-repo/semantics/closedAccess | |
dc.snmz | KA_WoS_20250125 | |
dc.subject | Dinitroaniline | |
dc.subject | Prodrug | |
dc.subject | Ssap-NtrB | |
dc.subject | Nitroreductase | |
dc.subject | Enzymatic activity | |
dc.subject | Cytotoxicity | |
dc.subject | Prostate cancer | |
dc.subject | In silica studies | |
dc.title | 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 | |
dc.type | Article |