Studies on synthesis and biological effects of 1-phenyl-2-(1H-imidazol-1-yl) ethanone oxime esters

In this study, a series of 1-phenyl-2-(1H-imidazol-1-yl) ethanone oxime ester derivatives that are designed based on the general structure of azole group antifungals was synthesized. Their structures were elucidated by using spectral methods and elemental analysis results and also, antibacterial and antifungal activities were evaluated. The antibacterial activities of all compounds against studied Gram (+) and Gram (-) bacteria were found to be very low compared to the standard compound gentamicin. Sorbic acid ester derivative, compound 5c, (MIC: 4 µg/mL) was found to show similar activity against to C. albicans and C. parapsilosis to the standard compound fluconazole (MIC: 0,5 µg/mL). The structure-activity relationship between the type and the length of the alkyl chain of the oxime ester structure and the antifungal activity was investigated; however, no clear relationship could be established between the structural properties of the alkyl chain and the antifungal activity. Molecular docking studies were performed in the light of crystallographic data, which provide detailed insights into binding and molecular determinants of azoles in CYP51 binding site. Molecular docking studies showed that compound 5c fit in the active site of CACYP51 and fulfilled the molecular determinants for the enzyme's inhibition, in line with the fact that azole antifungals inhibit fungal CYP51. Keywords: (aryllalkyl)azole, oxime ester, antifungal, antibacterial, moleküler docking This study was funded by The Scientific and Technological Research Council of Turkey (TÜBİTAK) (Grant no: 113S060) ve Hacettepe UniversityScientific Research Projects Coordination Unit (Grant no: TDK- 2017-14965, 014 D09 301 001-703, and TPT-2015-6794).