Studies on new oxime ester derivatives in (arylalkyl)azole structure: Synthesis, biological activity, and molecular modelling

In this study, a set of novel oxime esters in (arylalkyl)azole structure were designed based on azole antifungals, especially oxiconazole, and synthesized by the reaction of 1-(4-chlorophenyl)-2-(1Himidazol/1H-1,2,4-triazol-1-yl)ethanone oxime with various carboxylic acids. Their structures and purity were confirmed via spectroscopic methods, X ray crystalloraphy, and elemental analyses. Their antimicrobial effects against some Candida sp. and bacteria were evaluated using microdilution and biofilm methods. Some of the compounds showed potent antifungal activity compared to the reference drugs. Due to the structural similarities between azole antifungals and (arylalkyl)azole anticonvulsants, the compounds were screened in vivo by NIH Epilepsy Therapy Screening Program (ETSP) for their anticonvulsant activities. Most of the compounds were found protective against certain seizure types in anticonvulsant identification and quantification tests. In molecular modeling studies, the compounds were found similar to known drugs regarding their physicochemical and pharmacokinetic properties. A homology model of lanosterol 14-α demethylase of C. albicans, the target enzyme of azole antifungals, was built and optimized, the affinity and binding interactions of the compounds of antifungal activity with the active site of this enzyme were predicted. Their affinities and binding interactions with one of the possible targets responsible with their anticonvulsant activities, type A GABA receptor, were predicted on a homology model obtained from the literature.