Gershon H, Shanks L, Gawiak D E
J Med Chem. 1976 Aug;19(8):1069-72. doi: 10.1021/jm00230a019.
Twenty-three 4-substituted crotonic acid esters were tested for antifungal activity against Candida albicans, Aspergillus niger, Mucor mucedo, and Trichophyton mentagrophytes. For the analogues of the methyl ester containing substituents in the 4 position, the following order of fungitoxicity was observed: I greater than Br greater than Cl greater than CH3S greater than CH3O greater than F=H. Of the homologues of the esters of the 4-iodo and 4-bromo compounds which included methyl, ethyl, n-propyl, n-butyl, n-pentyl, and n-hexyl, ethyl 4-iodocrotonate was most toxic to the four fungi at pH 7.0 in the presence of 10% beef serum (C. albicans, 18mug/ml, A. niger, 40 mug/ml, M. mucedo, 5 mug/ml, T. mentagrophytes, 4 mug/ml). It is believed that the mechanism of fungitoxicity is due, in part, to a nucleophilic reaction involving SH-containing compounds. This is based on the correlation of fungitoxicity with the order of leaving groups in the nucleophilic reaction and the protection against the toxicity of the test compounds to the fungi by cysteine and glutathione.
对23种4-取代巴豆酸酯进行了抗真菌活性测试，测试对象为白色念珠菌、黑曲霉、毛霉和须癣毛癣菌。对于在4位含有取代基的甲酯类似物，观察到以下真菌毒性顺序：碘＞溴＞氯＞甲硫基＞甲氧基＞氟 = 氢。在4-碘代和4-溴代化合物的酯同系物中，包括甲酯、乙酯、正丙酯、正丁酯、正戊酯和正己酯，在pH 7.0、10%牛血清存在的条件下，4-碘代巴豆酸乙酯对这四种真菌的毒性最大（白色念珠菌，18μg/ml；黑曲霉，40μg/ml；毛霉，5μg/ml；须癣毛癣菌，4μg/ml）。据信，真菌毒性机制部分归因于涉及含硫氢化合物的亲核反应。这是基于真菌毒性与亲核反应中离去基团顺序的相关性，以及半胱氨酸和谷胱甘肽对测试化合物对真菌毒性的保护作用。
