Structureactivity relationships of antifungal phenylpropanoid derivatives and their synergy with n-dodecanol and fluconazole.
Structureactivity relationships of antifungal phenylpropanoid derivatives and their synergy with n-dodecanol and fluconazole.
复制标题
抗真菌苯丙素衍生物的结构活性关系及其与正十二烷醇和氟康唑的协同作用。
DOI：
10.1111/lam.13613
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发表时间：
2022
影响因子：
2.4
通讯作者：
Fujita K
中科院分区：
文献类型：
--
作者：
Tsukuda Y;Mizuhara N;Usuki Y;Yamaguchi Y;Ogita A;Tanaka T;Fujita K
反式茴香脑（茴香脑）是一种苯丙素;与其他药物一起，它对几种真菌表现出协同活性，预计将用于引起较少患者副作用的新疗法。然而，负责这种协同作用的分子的详细子结构尚未完全阐明。我们研究了苯丙素类化合物及其衍生物的构效关系，特别关注了茴香脑中的甲氧基和丙烯基的双键，以及对烷基苯甲醚中对烷基链的长度。抗真菌效力在很大程度上与茴香脑的顶烷基链长度和甲氧基有关，但与其丙烯基的双键无关。活性氧的产生也在这些杀真菌活性中发挥了作用。药物外排的抑制作用与茴香脑中丙烯基的对-烷基链和双键的长度有关，但与甲氧基无关。尽管在正十二烷醇和茴香脑或烷基链长度为C2-C6的对烷基苯甲醚之间观察到理想的协同作用，但不能将其解释为仅仅是由于药物外排的抑制。苯丙素类衍生物与氟康唑联合应用对白色念珠菌也有类似的效果。
trans‐Anethole (anethole) is a phenylpropanoid; with other drugs, it exhibits synergistic activity against several fungi and is expected to be used in new therapies that cause fewer patient side effects. However, the detailed substructure(s) of the molecule responsible for this synergy has not been fully elucidated. We investigated the structure–activity relationships of phenylpropanoids and related derivatives, with particular attention on the methoxy group and the double bond of the propenyl group in anethole, as well as the length of thep‐alkyl chain inp‐alkylanisoles. Antifungal potency was largely related top‐alkyl chain length and the methoxy group of anethole, but not to the double bond of its propenyl group. Production of reactive oxygen species also played a role in these fungicidal activities. Inhibition of drug efflux was associated with the length of thep‐alkyl chain and the double bond of the propenyl group in anethole, but not with the methoxy group. Although a desirable synergy was observed betweenn‐dodecanol and anethole orp‐alkylanisoles with a length of C2–C6 in alkyl chains, it cannot be explained away as being solely due to the inhibition of drug efflux. Similar results were obtained when phenylpropanoid derivatives were combined with fluconazole againstCandida albicans.