Pyrrole derivatives as potential anti-cancer therapeutics: synthesis, mechanisms of action, safety.

摘要: Pyrrole derivatives (PDs) chloro-1-(4-chlorobenzyl)-4-((3-(trifluoromethyl)phenyl)amino)-1H-pyrrole-2,5-dione (MI-1) and 5-amino-4-(1,3-benzothyazol-2-yn)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrole-3-one (D1) were synthesised as inhibitors of several protein kinases including EGFR VEGFR. The aim the study was to reveal exact mechanisms PDs' action VEGFR are involved in. We observed, that both PDs could bind with form stable complexes. entered into electrostatic interactions polar groups phospholipid heads in cell membrane, power interaction depended on nature PD radical substituents (greater for MI-1 smaller D1). Partial intercalation membrane hydrophobic zone also occurred. concentrations induced apoptosis malignant cells but normal ones had different sensitivity those. D1 acted like antioxidants inflamed colonic tissue, evidenced by reduce lipid peroxidation products (by 43-67%) increase superoxide dismutase activity 40 58%) restoring these values control ones. restored reduced haemoglobin normalised elevated platelets monocytes settings colorectal cancer, whereas only platelets. Thus, be used competitive antioxidants, which might contribute realisation their anti-inflammatory, proapoptotic antitumor activity.