title: In vitro antifungal activities of D11-2040, a beta-1,6-glucan inhibitor, with or without currently available antifungal drugs.
abstract: 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.
authors.affiliation: R&D Division, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. kitamura.akihiro.cr@daiichisankyo.co.jp
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kitamura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Someya
authors.forename: Ryo
authors.initials: R
authors.lastname: Okumura
authors.forename: Masato
authors.initials: M
authors.lastname: Hata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshita
authors.forename: Ryohei
authors.initials: R
authors.lastname: Nakajima
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D001562:Benzimidazoles; C539939:D75-4590; D011725:Pyridines; D047071:beta-Glucans; C064197:beta-1,6-glucan