Core-modified sordaricin derivatives: synthesis and antifungal activity.
Core-modified sordaricin derivatives were prepared via biotransformation followed by chemical modification and tested for antifungal activity. The antifungal activity proved to be very sensitive to modifications in the sterics and/or lipophilicity of the diterpene skeleton. Introduction of polar groups such as hydroxyl in the diterpene core results in loss of potency while small and lipophilic groups such as fluorine and the 7,8-olefin are well tolerated.
Regueiro-Ren
Alicia
A
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492, USA. alicia.regueiroren@bms.com
Carroll
Tina M
TM
Chen
Yijun
Y
Matson
James A
JA
Huang
Stella
S
Mazzucco
Charles E
CE
Stickle
Terry M
TM
Vyas
Dolatrai M
DM
Balasubramanian
Balu N
BN
D000935:Antifungal Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001711:Biotransformation; D002176:Candida albicans / Q000187:drug effects; D041221:Candida glabrata / Q000187:drug effects; D004224:Diterpenes; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D009615:Nocardia / Q000378:metabolism; D013237:Stereoisomerism
D000935:Antifungal Agents; D004224:Diterpenes; C116705:sordaricin