Gul H I, Ojanen T, Vepsalainen J, Gul M, Erciyas E, Hanninen O
Department of Chemistry, University of Kuopio, Kuopio, Finland.
Arzneimittelforschung. 2001 Jan;51(1):72-5. doi: 10.1055/s-0031-1300005.
The development of resistance to current antifungal therapeutics drives search for new effective agents. Some Mannich bases have antifungal activity, but no information is available regarding the antifungal activity of acetophenone derived Mannich bases. Mono Mannich bases of acetophenone 1-3 were synthesized and converted into their corresponding bis derivatives, 5-7. Representative quaternary derivatives 4 and 8 were also synthesized. Antifungal activities of the compounds were evaluated using some yeasts and dermatophytes in vitro. Mono Mannich base 3 and quaternary compounds 4 and 8 were found to be 2-16 times more potent than the reference compound amphotericin B against dermatophytes: Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum canis. Compounds 4 and 8 were also found to be 2 times more effective compared with amphotericin B against the yeast Saccharomyces cerevisiae. Quaternization procedure improved the biological activity dramatically, whereas conversion of mono Mannich bases to corresponding bis derivatives generally did not affect antifungal activity. Our results suggest that acetophenone derived mono Mannich base 3 and quaternary derivatives 4 and 8 may serve as leading compounds for further studies to develop new antifungal agents with their highly potent antifungal activity.
对当前抗真菌治疗药物产生耐药性促使人们寻找新的有效药物。一些曼尼希碱具有抗真菌活性，但关于苯乙酮衍生的曼尼希碱的抗真菌活性尚无相关信息。合成了苯乙酮的单曼尼希碱1 - 3，并将其转化为相应的双衍生物5 - 7。还合成了代表性的季铵衍生物4和8。使用一些酵母和皮肤癣菌在体外评估了这些化合物的抗真菌活性。发现单曼尼希碱3以及季铵化合物4和8对皮肤癣菌红色毛癣菌、须癣毛癣菌和犬小孢子菌的效力比参考化合物两性霉素B高2至16倍。还发现化合物4和8对酿酒酵母的效力是两性霉素B的2倍。季铵化过程显著提高了生物活性，而将单曼尼希碱转化为相应的双衍生物通常不影响抗真菌活性。我们的结果表明，苯乙酮衍生的单曼尼希碱3以及季铵衍生物4和8因其高效的抗真菌活性，可能作为进一步研究开发新型抗真菌药物的先导化合物。
