R&D Division, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Biol Pharm Bull. 2010;33(2):192-7. doi: 10.1248/bpb.33.192.
We recently reported our discovery of small molecule beta-1,6-glucan inhibitor named D75-4590 and the anti-Candida activity of its derivatives D11-2040 and D21-6076. In this study, we further evaluated the antifungal profile of D11-2040. It alone strongly inhibited the vegetative growth and/or hyphal development of various Candida species, but no significant activity was observed against Cryptococcus neoformans or any of the filamentous fungi tested. Synergism was detected for C. albicans in the interaction of D11-2040 and caspofungin by the chequerboard method and in that of D11-2040 and fluconazole by the time-kill method. Slight but positive interactions were observed in several combinations for C. neoformans and Aspergillus fumigatus as well. These results suggested that beta-1,6-glucan inhibitors have promising potential as single drugs as well as concomitants.
我们最近报道了小分子β-1,6-葡聚糖抑制剂 D75-4590 的发现及其衍生物 D11-2040 和 D21-6076 的抗假丝酵母菌活性。在本研究中,我们进一步评估了 D11-2040 的抗真菌谱。它单独强烈抑制各种假丝酵母菌的营养生长和/或菌丝发育,但对新生隐球菌或任何测试的丝状真菌均无明显活性。棋盘法检测到 D11-2040 与卡泊芬净对白色念珠菌存在协同作用,时间杀伤法检测到 D11-2040 与氟康唑存在协同作用。对于新生隐球菌和烟曲霉,在几种组合中也观察到轻微但阳性的相互作用。这些结果表明,β-1,6-葡聚糖抑制剂具有作为单药和伴随药物的潜在前景。