Prodrugs for nitroreductase based cancer therapy-4: Towards prostate cancer targeting: Synthesis of N-heterocyclic nitro prodrugs, Ssap-NtrB enzymatic activation and anticancer evaluation

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dc.authoridGungor, Tugba/0000-0001-5261-1856
dc.authoridAY, Mehmet/0000-0002-1095-1614
dc.contributor.authorGungor, Tugba
dc.contributor.authorTokay, Esra
dc.contributor.authorGulhan, Unzile Guven
dc.contributor.authorHacioglu, Nelin
dc.contributor.authorCelik, Ayhan
dc.contributor.authorKockar, Feray
dc.contributor.authorAy, Mehmet
dc.date.accessioned2025-01-27T20:53:50Z
dc.date.available2025-01-27T20:53:50Z
dc.date.issued2020
dc.departmentÇanakkale Onsekiz Mart Üniversitesi
dc.description.abstractIn this study, various N-heterocyclic nitro prodrugs (NHN1-16) containing pyrimidine, triazine and piperazine rings were designed and synthesized. The final compounds were identified using FT-IR, H-1 NMR, C-13 NMR as well as elemental analyses. Enzymatic activities of compounds were conducted by using HPLC analysis to investigate the interaction of substrates with Ssap-NtrB nitroreductase enzyme. MTT assay was performed to evaluate the toxic effect of compounds against Hep3B and PC3 cancer cell lines and healthy HUVEC cell. It was observed that synthesized compounds NHN1-16 exhibited different cytotoxic profiles. Pyrimidine derivative NHN3 and triazine derivative NHN5 can be good drug candidates for prostate cancer with IC50 values of 54.75 mu M and 48.9 mu M, respectively. Compounds NHN6, NHN10, NHN12, NHN14 and NHN16 were selected as prodrug candidates because of non-toxic properties against three different cell models. The NHN prodrugs and Ssap-NtrB combinations were applied to SRB assay to reveal the prodrug capabilities of these selected compounds. SRB screening results showed that the metabolites of all selected non-toxic compounds showed remarkable cytotoxicity with IC50 values in the range of 1.71-4.72 nM on prostate cancer. Among the tested compounds, especially piperazine derivatives NHN12 and NHN14 showed significant toxic effect with IC50 values of 1.75 nM and 1.79 nM against PC3 cell compared with standart prodrug CB1954 (IC50: 1.71 nM). Novel compounds NHN12 and NHN14 can be considered as promising prodrug candidates for nitroreductase-prodrug based prostate cancer therapy.
dc.description.sponsorshipTUBITAK (Scientific and Technological Research Council of Turkey) [113Z706]
dc.description.sponsorshipThis study was financially supported by TUBITAK (Scientific and Technological Research Council of Turkey) with Grant No: 113Z706.
dc.identifier.doi10.1016/j.bioorg.2020.104450
dc.identifier.issn0045-2068
dc.identifier.issn1090-2120
dc.identifier.pmid33189994
dc.identifier.scopus2-s2.0-85095941388
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.bioorg.2020.104450
dc.identifier.urihttps://hdl.handle.net/20.500.12428/25862
dc.identifier.volume105
dc.identifier.wosWOS:000603573200001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAcademic Press Inc Elsevier Science
dc.relation.ispartofBioorganic Chemistry
dc.relation.publicationcategoryinfo:eu-repo/semantics/openAccess
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WoS_20250125
dc.subjectPyrimidine
dc.subjectTriazine
dc.subjectPiperazine
dc.subjectNitro compounds
dc.subjectNitroreductase
dc.subjectGDEPT
dc.subjectProstate cancer
dc.titleProdrugs for nitroreductase based cancer therapy-4: Towards prostate cancer targeting: Synthesis of N-heterocyclic nitro prodrugs, Ssap-NtrB enzymatic activation and anticancer evaluation
dc.typeArticle

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