DST-FIST Sponsored School of Life Sciences, SRTM University, Nanded 431606, MS, India.
Phytomedicine. 2011 Oct 15;18(13):1181-90. doi: 10.1016/j.phymed.2011.03.008. Epub 2011 May 19.
Anti-Candida potential of six terpenoids were evaluated in this study against various isolates of Candida albicans (n=39) and non-C. albicans (n=9) that are differentially susceptible to fluconazole. All the six terpenoids tested, showed excellent activity and were equally effective against isolates of Candida sps., tested in this study. Linalool and citral were the most effective ones, inhibiting all the isolates at ≤0.064% (v/v). Five among the six terpenoids tested were fungicidal. Time dependent kill curve assay showed that MFCs of linalool and eugenol were highly toxic to C. albicans, killing 99.9% inoculum within seven min of exposure, while that of citronellal, linalyl acetate and citral required 15min, 1h and 2h, respectively. FIC index values (Linalool - 0.140, benzyl benzoate - 0.156, eugenol - 0.265, citral - 0.281 and 0.312 for linalyl acetate and citronellal) and isobologram obtained by checker board assay showed that all the six terpenoids tested exhibit excellent synergistic activity with fluconazole against a fluconazole resistant strain of C. albicans. Terpenoids tested arrested C. albicans cells at different phases of the cell cycle i.e. linalool and LA at G1, citral and citronellal at S phase and benzyl benzoate at G2-M phase and induced apoptosis. Linalool, citral, citronellal and benzyl benzoate caused more than 50% inhibition of germ tube induction at 0.008%, while eugenol and LA required 0.032 and 0.016% (v/v) concentrations, respectively. MICs of all the terpenoids for the C. albicans growth were non toxic to HeLa cells. Terpenoids tested exhibited excellent activity against C. albicans yeast and hyphal form growth at the concentrations that are non toxic to HeLa cells. Terpenoids tested in this study may find use in antifungal chemotherapy, not only as antifungal agents but also as synergistic agents along with conventional drugs like fluconazole.
本研究评估了六种萜类化合物对不同氟康唑敏感性的白色念珠菌（n=39）和非白色念珠菌（n=9）分离株的抗念珠菌潜力。在这项研究中测试的六种萜类化合物均表现出优异的活性，对测试的念珠菌分离株同样有效。芳樟醇和柠檬醛是最有效的两种，抑制所有分离株的浓度均≤0.064%（v/v）。在测试的六种萜类化合物中，有五种具有杀菌作用。时间依赖性杀伤曲线试验表明，芳樟醇和丁香酚的 MFC 对白色念珠菌具有高度毒性，暴露 7 分钟内即可杀死 99.9%的接种物，而柠檬醛、乙酸芳樟酯和柠檬醛分别需要 15 分钟、1 小时和 2 小时。FIC 指数值（芳樟醇为 0.140、苯甲酸苄酯为 0.156、丁香酚为 0.265、柠檬醛为 0.281 和乙酸芳樟酯和柠檬醛为 0.312）和棋盘试验获得的等对图表明，测试的六种萜类化合物均与氟康唑对氟康唑耐药的白色念珠菌表现出优异的协同活性。测试的萜类化合物使白色念珠菌细胞在细胞周期的不同阶段停滞，即芳樟醇和 LA 在 G1 期，柠檬醛和柠檬醛在 S 期，苯甲酸苄酯在 G2-M 期，并诱导细胞凋亡。芳樟醇、柠檬醛、柠檬烯和苯甲酸苄酯在 0.008%时引起超过 50%的芽管诱导抑制，而丁香酚和 LA 分别需要 0.032%和 0.016%（v/v）浓度。所有萜类化合物对白色念珠菌生长的 MIC 对 HeLa 细胞均无毒性。在对 HeLa 细胞无毒的浓度下，测试的萜类化合物对白色念珠菌酵母和菌丝形式的生长表现出优异的活性。在这项研究中测试的萜类化合物不仅可以作为抗真菌药物，而且可以作为与氟康唑等传统药物协同作用的药物，在抗真菌化学疗法中可能有一定的应用。
