A novel polyamide SL-A92 as a potential fungal resistance blocker: synthesis and bioactivities in Candida albicans

作者：Zhu Shao long; Jiang Zhi hui; Gao Ping hui; Qiu Yue; Wang Liang; Jiang Yuan ying^*; Zhang Da zhi

来源：Acta Pharmacologica Sinica, 2010, 31(7): 855-860.

DOI：10.1038/aps.2010.59

• Candida albicans
• drug resistance
• CDR
• polyamide
• SL-A92
• fluconazole

Aim: To synthesize a novel polyamide SL-A92 and evaluate its bioactivity against drug resistance in Candida albicans.
Methods: SL-A92 was synthesized using N-hydroxybenzotriazole (HOBT)/N, N'-dicyclohexylcarbodiimide (DCC) in solution phase. Its antifungal activities and effects on strain growth were tested using the micro-broth dilution method and growth curves, respectively. Induced drug resistance in the C. albicans collection strain SC5314 was obtained by incubation with fluconazole (12 mu g/mL) for 21 passages. Meanwhile, incubations with SL-A92 plus fluconazole were also carried out in SC5314 strains, and the MIC(80)s were used to evaluate the inhibitory effects of SL-A92 on drug resistance during the induction process. Real time RT-PCR was performed to investigate the CDR1 and CDR2 mRNA levels in induced SC5314 strains.
Results: SC5314 strain induced by the combination of fluconazole and SL-A92 (200 mu g/mL) did not develop drug resistance. On day 24, the CDR1 and CDR2 mRNA levels in SC5314 strain co-treated with fluconazole and SL-A92 relative to fluconazole alone were 26% and 24%, respectively, and on day 30 the CDR1 and CDR2 mRNA levels were 43% and 31%, respectively.
Conclusion: SL-A92 can block the development of drug resistance during the fluconazole induction process, which partially results from the down-regulation of CDR1 and CDR2.

• 出版日期2010-7
• 单位复旦大学; 中国人民解放军第二军医大学