含氨基酸或小肽的阳离子抗菌药物  

Cationic antimicrobial agents containing amino acids or small peptides

作　　者：王艳[1] 吴条 唐美 邹俊娜 WANG Yan;WU Tiao;TANG Mei;ZOU Jun-na(School of Chemistry and Chemical Engineering,Central South University,Changsha 410083)

机构地区：[1]中南大学化学化工学院,长沙410083

出　　处：《中南药学》2022年第8期1786-1792,共7页Central South Pharmacy

基　　金：湖南省自然科学基金项目(No.2018JJ2491)。

摘　　要：目的针对念珠性阴道炎研究不易诱导耐药菌产生的抗菌药物。方法本文合成了两类阳离子两亲性化合物:短脂肽(SSLP)和氨基酸基阳离子表面活性剂(AACS),并以经典阳离子表面活性剂(CCS)为对照,从抑菌活性、诱导耐药菌产生、溶血率、对哺乳动物细胞毒性等四个方面进行研究,然后通过稳定性和多次阴道刺激性实验确定针对念珠性阴道炎最有效的候选药物。结果SSLP和CCS都有良好的杀菌活性,但是对于人阴道上皮细胞株VK2/E6E7具有较高的细胞毒性,而SSLP不易诱导细菌产生耐药性,所以外用杀菌消毒如器械消毒时,SSLP是CCS的理想替代品。AACS中的N^(α)-月桂酰基精氨酸乙酯(C12-R-OEt)对于白色念珠菌敏感,不易诱导耐药菌的产生,安全性高,在接近阴道环境pH 4的水溶液中稳定,对阴道黏膜无刺激性。结论C12-R-OEt是最有潜力的念珠性阴道炎外用候选药物。Objective To determine the new antimicrobial agents with low drug resistance in treating vulvovaginal candidiasis.Methods We synthesized two categories of cationic amphiphilic compounds:short synthesized lipopeptides(SSLP)and amino acid-based cationic surfactants(AACS).Classical cationic surfactants(CCS)was used as references,and we tested the two categories as to antimicrobial activity,resistance development,hemolytic activity and toxicity to mammalian.Then we conducted stability evaluation and rabbit vaginal irritation tests to identify the most potent candidate for vulvovaginal candidiasis.Results SSLP and CCS both showed good antimicrobial activity but high cytotoxicity to human vaginal epithelial cells VK2/E6E7.SSLP displayed low resistance,making it an ideal alternative for CCS in external sterilization and apparatus disinfection.N^(α)-lauryl arginine ethyl ester(C12-R-OEt),one type of AACA,was sensitive to Candida albicans,and highly unlikely to induce resistant pathogenic microbes.It was safe,stable in aqueous solution at pH 4,without vaginal irritation.Conclusion C12-R-OEt is the most potent candidate for effective treatment of vulvovaginal candidiasis.

关 键 词：念珠性阴道炎 短抗菌脂肽 N^(α)-酰基精氨酸乙酯 苯扎溴铵 醋酸氯己定 

分 类 号：R96[医药卫生—药理学] R914[医药卫生—药学]