In vitro antifungal activities of D11-2040, a beta-1,6-glucan inhibitor, with or without currently available antifungal drugs.
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.
Kitamura
Akihiro
A
R&D Division, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. kitamura.akihiro.cr@daiichisankyo.co.jp
Someya
Kazuhiko
K
Okumura
Ryo
R
Hata
Masato
M
Takeshita
Hiroshi
H
Nakajima
Ryohei
R
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000502:physiology; D001562:Benzimidazoles / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects / Q000502:physiology; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000502:physiology; D004359:Drug Therapy, Combination; D005260:Female; D051379:Mice; D008826:Microbial Sensitivity Tests / Q000379:methods; D011725:Pyridines / Q000494:pharmacology*; D047071:beta-Glucans / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000935:Antifungal Agents; D001562:Benzimidazoles; C539939:D75-4590; D011725:Pyridines; D047071:beta-Glucans; C064197:beta-1,6-glucan