“Syntheses of Bleomycin Ligand Models Containing Carbohydrates with Antitumor Activities and Investigation of Reactivity Properties of Non-heme High-Valent Iron(IV)-Oxo Complexes”
Project no. 463 · Status: Kapanmış · 2017
Summary
Bleomycin (BLM) is an important natural antibiotic molecule that contains carbohydrate units and nucleophilic nitrogen atoms in its structure and has an anti-tumor activity that has clinical use for more than 50 years. The effects of the carbohydrate domain in BLM on recognition and targeting of tumor cells have been determined, but its role on activity is not fully understood. Therefore, researches on the carbohydrate domain in BLM are required and became an area of interest. As a synthesis strategy in this study, Novel BLM bio-inspired models bearing two carbohydrate units were formed from the ring opening reaction with homopiperazine or piperazine or ethylenediamine as a diamine skeleton, following the synthesis of the corresponding epoxy carbohydrate derivatives from D-glucochloralose, D-galactochloralose, diacetone-D-glucose and diacetone-D-galactose monosaccharides containing protecting groups. The biomimetic compounds were obtained as a hybrid design of the metal binding and carbohydrate domain in BLM anti-tumor drug. Subsequently, the structures of the obtained compounds were characterized by FT-IR, 1H-NMR, 13C-NMR, 2D-NMR (HSQC, HMBC and COSY) spectroscopic methods. Cytotoxicity studies of new model compounds were conducted with regard to investigation of biological activities. Anti-tumor activity properties were found in the five models (Glc-chls-3-O-L6, Glc-chls-3-O-L7, Gal-chls-3-O-L2, Gal-chls-3-O-L6, Gal-chls-3-O-L7) among BLM biomimetic compounds.