Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu Universty, 26470 Eskişehir, Turkey.
Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu Universty, 26470 Eskişehir, Turkey.
Molecules. 2018 Apr 4;23(4):831. doi: 10.3390/molecules23040831.
In the present work, 15 new 1-(4-(1-imidazol-1-yl)phenyl)-3-(4-substituedphenyl)prop-2-en-1-one derivatives (−) were synthesized to evaluate their antifungal activity. Structures of newly synthesized imidazole derivatives (−) were characterized by IR, ¹H-NMR, C-NMR, and LCMSMS spectroscopic methods. The anticandidal activity of compounds (−) against (ATCC 24433), (ATCC 6258), (ATCC 22019), and (ATCC 90030) was elucidated according to the EUCAST definitive (EDef 7.1) method. Consistent with the activity studies, − were found to be more potent derivatives with their MIC values (0.78 µg/mL−3.125 µg/mL) against strains. Compound indicated similar antifungal activity to ketoconazole against all species and was evaluated as the most active derivative in the series. Effects of the most potent derivatives − on ergosterol biosynthesis were observed by LC-MS-MS method, which is based on quantification of the ergosterol level in . 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 were performed to evaluate its binding modes on lanosterol 14-α-demethylase. In addition to in vitro tests, docking studies also revealed that Compound is a potential ergosterol biosynthesis inhibitor.
在本工作中，我们合成了 15 种新的 1-(4-(1-咪唑基)苯基)-3-(4-取代苯基)丙-2-烯-1-酮衍生物（−），以评估它们的抗真菌活性。新合成的咪唑衍生物（−）的结构通过红外光谱（IR）、1H-NMR、C-NMR 和 LCMSMS 光谱方法进行了表征。根据 EUCAST 明确（Edef 7.1）方法，通过抗真菌活性研究，阐明了化合物（−）对（ATCC 24433）、（ATCC 6258）、（ATCC 22019）和（ATCC 90030）的抗真菌活性。与活性研究一致，− 被发现是具有较强活性的衍生物，其 MIC 值（0.78 µg/mL-3.125 µg/mL）对菌株有效。化合物对所有 种真菌均表现出与酮康唑相似的抗真菌活性，被评估为该系列中最具活性的衍生物。通过 LC-MS-MS 方法观察到最有效衍生物（−）对麦角甾醇生物合成的影响，该方法基于 中麦角甾醇水平的定量。此外，这些化合物进行了细胞毒性测试，以初步评估其毒性概况，发现它们是非细胞毒性的。此外，还对最活跃的衍生物 进行了对接研究，以评估其在羊毛甾醇 14-α-脱甲基酶上的结合模式。除了体外测试外，对接研究还表明，化合物 是一种潜在的麦角甾醇生物合成抑制剂。
