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

GÜNGÖR T., CÖMERT ÖNDER F., Tokay E., Gulhan U. G., Hacioglu N., Tok T. T., ...Daha Fazla

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, cilt.171, ss.383-400, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 171
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1016/j.ejmech.2019.03.035
  • Dergi Adı: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.383-400
  • Anahtar Kelimeler: Nitro aromatic amides, Prodrug, Ssap-NtrB, Enzymatic activity, Cytotoxicity, Molecular docking
  • Çanakkale Onsekiz Mart Üniversitesi Adresli: Evet

Özet

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 prodrugiNTR 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. (C) 2019 Elsevier Masson SAS. All rights reserved.