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.
- 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: [email protected].
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.