2. Academic Validation
  3. PRODRUGS FOR NITROREDUCTASE BASED CANCER THERAPY- 2: Novel amide/Ntr combinations targeting PC3 cancer cells

PRODRUGS FOR NITROREDUCTASE BASED CANCER THERAPY- 2: Novel amide/Ntr combinations targeting PC3 cancer cells

  • Eur J Med Chem. 2019 Jun 1:171:383-400. doi: 10.1016/j.ejmech.2019.03.035.
Tuğba Güngör 1,  Ferah Cömert Önder 1,  Esra Tokay 2,  Ünzile Güven Gülhan 3,  Nelin Hacıoğlu 2,  Tuğba Taşkın Tok 4,  Ayhan Çelik 3,  Feray Köçkar 2,  Mehmet Ay 5
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Sciences and Arts, Natural Products and Drug Research Laboratory, Çanakkale Onsekiz Mart University, Çanakkale, 17020, Turkey.
  • 2 Department of Molecular Biology and Genetic, Faculty of Sciences and Arts, Balıkesir University, Balıkesir, 10145, Turkey.
  • 3 Department of Chemistry, Faculty of Science, Gebze Technical University, Gebze, Kocaeli, 41400, Turkey.
  • 4 Department of Chemistry, Faculty of Sciences and Arts, Gaziantep University, Gaziantep, 27310, Turkey.
  • 5 Department of Chemistry, Faculty of Sciences and Arts, Natural Products and Drug Research Laboratory, Çanakkale Onsekiz Mart University, Çanakkale, 17020, Turkey. Electronic address: mehmetay06@comu.edu.tr.
PMID: 30928710 DOI: 10.1016/j.ejmech.2019.03.035
Abstract

The use of nitroreductases (NTR) that catalyze the reduction of nitro compounds by using NAD(P)H in GDEPT (Gene-directed Enzyme prodrug therapy) studies which minimize toxicity at healthy cells and increases concentration of drugs at Cancer cells is remarkable. Discovery of new prodrug/NTR combinations is necessary to be an alternative to known prodrug candidates such as CB1954, SN23862, PR-104A. For this aim, nitro containing aromatic amides (A1-A23)2 were designed, synthesized, performed in silico ADMET and molecular docking techniques in this study. Prodrug candidates were studied on reduction potentials with Ssap-NtrB by HPLC system. Also, cyototoxic properties and prodrug ability of these amides were investigated using different Cancer cell lines such as Hep3B and PC3. As a result of theoretical and biological studies, combinations of A5, A6 and A20 with Ssap-NtrB can be suggested as potential prodrugs/Enzyme combinations at NTR based Cancer therapy compared with CB1954/NfsB.

Keywords

Cytotoxicity; Enzymatic activity; Molecular docking; Nitro aromatic amides; Prodrug; Ssap-NtrB.

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