Dr. Tuğba Güngör graduated as BSc at Chemistry Department of Ankara University in 2007 and graduated as MSc in in 2010 under supervision of Dr. Mustafa GÜLLÜ and PhD in 2016 at Chemistry Department of Çanakkale Onsekiz Mart University under supervision of Dr. Mehmet AY. During the PhD education, worked at Dr. Rich Carter’s Research Lab. at Chemistry Department of Oregon State University at USA for 6 months at 2015. Since 2011, works as a research assistant at Chemistry Department of Çanakkale Onsekiz Mart University and going on research activities in Natural Products and Drug Research Laboratory, focusing on developing new prodrug and drug molecules for Cancer Therapy and other Medicinal Applications.
Nitroreductase enzymes catalyze the conversion of the nitro group of prodrug compounds via hydroxylamine to amine group and the active drug inhibits tumor formation by binding to DNA1,2. E. coli NTR/CB1954 (5-aziridinyl-2,4-dinitrobenzamide) is the best known combination that have studied phase I/II trial for different cancer types3. So more effective NTR/drug combination should be investigated for cancer therapies.
In this study, first of all, we explored and characterized two novel nitroreductases (Ssap-NtrB-cloned from a mesophilic microorganism and Gk-Ntr-cloned from a thermophilic microorganism) with enhanced activity-selectivity and implemented various applications4,5. And nitro group containing two potential prodrugs (isoxazole derivatives and 3,5-difluorophenyl derivatives) were synthesized and were investigated the interaction of these potential pro-drugs with NTR enzymes by spectroscopic techniques and HPLC analysis. Michaelis-Menten kinetic parameters were calculated for reduction reactions of prodrugs and compared common known prodrugs like as CB1954 and SN23862. The prodrugs were evaluated by MTT and SRB assay in three different cancer cell lines, Human Hepatoma Cancer (Hep3B), Human Colon Cancer (HT-29) and Human Prostate Cancer (PC3) in addition to non-cancer cell, HUVEC. According to our results, proposed enzyme/prodrug combinations may use NTR based cancer therapy.
Key Words: GDEPT, prodrugs, SSap-NTR, CB1954, metabolites, cytotoxicity.
Audience will learn:
•Learn the importance of nitroreductase to drug design and other applications,
•Synthesis of new prodrug candidates,
•Design new projects with collaboration for cancer therapy.