Design, synthesis, and biological activities of novel azole-bonded β-hydroxypropyl oxime O-ethers.

Abstract

The synthesis and biological effects of 15 novel azole-bonded β-hydroxypropyl oxime O-ethers have been described. In this synthesis, the oximation of aromatic ketones followed by an O-alkylation reaction with epichlorohydrin and/or epibromohydrin led to the corresponding O-oxime ether adducts. Subsequently, the attained O-oxime ether adducts were used to synthesize the target molecules after treating them with the appropriate azole derivatives. The in vitro antifungal and antibacterial activities of title compounds were obtained against several pathogenic fungi, Gram-positive and/or Gram-negative bacteria. Benzophenone O-2-hydroxy-3-(2-phenyl-1 H-imidazol-1-yl) propyl oxime and 9H-fluoren-9-one O-2-hydroxy-3-(2-phenyl-1 H-imidazol-1-yl)propyl oxime proved to have considerable antifungal activity against Candida albicans, Candida krusei, Aspergillus niger, and Trichophyton rubrum. These two compounds demonstrated comparable antifungal activity to clotrimazole and fluconazole (standard drugs). All compounds were also tested against Escherichia coli and Staphylococcus aureus as Gram-negative and Gram-positive bacteria, respectively, and their activities were compared to gentamycin and ampicillin (reference drugs). In general, marginal antibacterial activity against tested bacteria was observed for the title compounds. A molecular docking study is also discussed for the two most potent compounds against fungi. The docking study reveals a considerable interaction between the two most potent compounds and the active site of Mycobacterium P450DM. Moreover, these two compounds are much strongly bound to the active site of Mycobacterium P450DM compared to fluconazole.