Bioorganic and Medicinal Chemistry p. 6255 - 6269 (2004)
Update date:2022-08-04
Topics:
Nam, Nguyen-Hai
Sardari, Soroush
Selecky, Meredith
Parang, Keykavous
Carboxylic acid and phosphate ester derivatives of fluconazole were synthesized and evaluated in vitro against Cryptococcus neoformans, Candida albicans, and Aspergillus niger. Two classes of fluconazole derivatives, (a) carboxylic acid esters and (b) fatty alcohol and carbohydrate phosphate esters, were synthesized and evaluated in vitro against Cryptococcus neoformans, Candida albicans, and Aspergillus niger. All carboxylic acid ester derivatives of fluconazole (1a-l), such as O-2-bromooctanoylfluconazole (1g, MIC = 111 μg/mL) and O-11-bromoundecanoylfluconazole (1j, MIC = 198 μg/mL), exhibited higher antifungal activity than fluconazole (MIC ≥ 4444 μg/mL) against C. albicans ATCC 14053 in SDB medium. Several fatty alcohol phosphate triester derivatives of fluconazole, such as 2a, 2b, 2f, 2g, and 2h, exhibited enhanced antifungal activities against C. albicans and/or A. niger compared to fluconazole in SDB medium. For example, 2-cyanoethyl-ω-undecylenyl fluconazole phosphate (2b) with MIC value of 122 μg/mL had at least 36 times greater antifungal activity than fluconazole against C. albicans in SDB medium. Methyl-undecanyl fluconazole phosphate (2f) with a MIC value of 190 μg/mL was at least 3-fold more potent than fluconazole against A. niger ATCC 16404. All compounds had higher estimated lipophilicity and dermal permeability than those for fluconazole. These results demonstrate the potential of these antifungal agents for further development as sustained-release topical antifungal chemotherapeutic agents.
View MoreContact:Tel:+86-29-88764861 Fax:+86-29-88764861
Address:Rm#2107, Block A, Epin Meidao Building, Gaoxin Rd, Hi-Tech Zone, Xi’an, China
Guangzhou Probig Fine Chemical Co., Ltd.
Contact:020-86297874
Address:No.2, 1/F, No.20, Hetai Road,Hebian Village, Baiyun District,Guangzhou,China
Tianjin Jingye Fine Chemicals Co., Ltd.
Contact:+86-15722078107; +86-22-26911407
Address:Bohua Fine Chemicals Base of Petrochemical Industry Park, Nanhuan Road, Dagang District, Tianjin, 300271, P. R. China
Changzhou Sunlight Pharmaceutical Co., Ltd.
Contact:+86-519-83131668;83139028;83138042;83137041
Address:JiuliStreet, Benniu Town Changzhou City, Jiangsu Province
Suzhou Howsine Biological Technology Co.,Ltd(expird)
website:http://www.howsine.com
Contact:86-512-67262751
Address:No 3,Weihua Road ,Suzhou Industrial Park ,Jiangsu ,China.
Doi:10.1016/S0040-4039(01)81932-8
(1981)Doi:10.1016/S0040-4039(01)81851-7
(1981)Doi:10.1021/jo00346a049
(1982)Doi:10.1016/S0040-4039(01)81907-9
(1981)Doi:10.1246/cl.1981.1579
(1981)Doi:10.1016/S0008-4182(01)80041-7
(1947)