Synthesis and Anticandidal Activity of New Imidazole-Chalcones

Abstract

In the present work, 15 new 1-(4-(1H-imidazol-1-yl)phenyl)-3-(4-substituedphenyl)prop-2-en-1-one derivatives (3a–3o) were synthesized to evaluate their antifungal activity. Structures of newly synthesized imidazole derivatives (3a–3o) were characterized by IR, 1H-NMR, 13C-NMR, and LCMSMS spectroscopic methods. The anticandidal activity of compounds (3a–3o) against C. albicans (ATCC 24433), C. krusei (ATCC 6258), C. parapsilosis (ATCC 22019), and C. glabrata (ATCC 90030) was elucidated according to the EUCAST definitive (EDef 7.1) method. Consistent with the activity studies, 3a–3d were found to be more potent derivatives with their MIC50 values (0.78 µg/mL–3.125 µg/mL) against Candida strains. Compound 3c indicated similar antifungal activity to ketoconazole against all Candida species and was evaluated as the most active derivative in the series. Effects of the most potent derivatives 3a–3d on ergosterol biosynthesis were observed by LC-MS-MS method, which is based on quantification of the ergosterol level in C. krusei. Moreover, these compounds were subjected to a cytotoxicity test for the preliminary toxicological profiles and were found as non-cytotoxic. Furthermore, docking studies for the most active derivative 3c were performed to evaluate its binding modes on lanosterol 14-α-demethylase. In addition to in vitro tests, docking studies also revealed that Compound 3c is a potential ergosterol biosynthesis inhibitor.

Recent Advances in Chalcones: Synthesis, Transformation and Pharmacological Activities

“…According to Ames MPF assay, compound 95 (4-Cl, 2,5-diCl) was found to be non-genotoxic against TA98 and TA100 with/without metabolic activation [23]. In another work, compound 96 shown similar anticandidal activity to ketoconazole against C. albicans (ATCC 24433), C. krusei (ATCC 6258), C. parapsilosis (ATCC 22019), and C. glabrata (ATCC 90030) and as found potential ergosterol biosynthesis inhibitor [36] ( Fig. 4).…”

“…Chalcones are multifunctional molecules that possess promising pharmacological activities. Chalcones have been found useful as anticancer [23][24][25], antioxidant [26][27][28][29], antiinflammatory [30][31][32], anti-microbial [23,[33][34][35][36], anti-tubercular [34,37,38], antileishmanial [39], antimalarial [40][41][42], anthelmintic [27], osteogenic activity [43]. This review article focuses on recent applications of Claisen-Schmidt condensation reaction employed in the synthesis of chalcone, its transformation to heterocyclic compounds and pharmacological activities.…”

Design, synthesis, biological evaluation, and docking studies of some novel chalcones as selective COX‐2 inhibitors

“…The resulting solid was filtered, washed with water to remove sodium hydroxide, and crystallized from ethanol to give compounds 1−9 in good yields (74%−86%). [ 29 ]…”

Synthesis and Antifungal Potential of Some Novel Benzimidazole-1,3,4-Oxadiazole Compounds

“…X-ray crystal structures of 14 α-sterol demethylase enzyme (PDB code: 5FSA) [54] were retrieved from the Protein Data Bank server (). The docking procedure was applied using Schrödinger Maestro [58] interface as in previously described by our research group [8,52,59,60].…”