Alkol Esteri Yapısındaki Yeni Azol Türevlerinin Sentezi, Biyolojik Aktiviteleri, Moleküler Modelleme Çalışmaları ve Yapı-Etki İlişkileri

Abstract

In this study, various carboxylic acid esters of 1-aryl-2-(1H-imidazol-1-yl/1H-1,2,4-triazol-1-yl)ethanol was synthesized in order to discovery new organic compounds with antimicrobial and anticholinesterase effects; antifungal, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme inhibitory effects were tested. As compounds simultaneously inhibiting cholinesterase and indolamine 2,3-dioxygenase 1 (IDO1)/tryptophan 2,3-dioxygenase 2 (TDO2) enzymes could actually be effective in the treatment of Alzheimer's Disease (AD) according to the literature studies, the IDO1/TDO2 enzyme inhibitory activities of the title compounds were screened and structure-activity relationships (SAR) were established. The SARs regarding cholinesterase inhibitory effects of the compounds were supported by molecular modeling studies. Since the toxic effects of antimicrobial agents on host cells should be minimal, the cytotoxic effects of active compounds on healthy cells were also tested. The target compounds were synthesized by esterification of various carboxylic acids with the alcohol derivatives, which were the reduction products of respective arylazoleethanones obtained by bromination of 1-aryletanone derivatives at position 2 followed by N-alkylation of the selected azole rings with the brominated derivatives. At the end of this thesis study, strong BChE and IDO1 inhibitory and low cytotoxic new azole compounds were found.