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

• Published in: Acta pharmacologica Sinica 2010 (7), p.855-860
• Main Author: Shao-Iong ZHU Zhi-hui JIANG Ping-hui GAO Yue QIU Liang WANG Yuan-ying JIANG Da-zhi ZHANG
• Format: Article
• Language: English
• Subjects: mRNA水平; 抗真菌; 生物活性; 聚酰胺; 诱导耐药性; 阻滞剂
• ISSN: 1671-4083; 1745-7254

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 μg/mL） for 21 passages. Meanwhile, incubations with SL-A92 plus fluconazole were also carried out in SC5314 strains, and the MIC50s 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 μg/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.