Synthesis and biological evaluation of trehalose analogs as potential inhibitors of mycobacterial cell wall biosynthesis.
Analogs of trehalose are reported that were designed to interfere with mycolylation pathways in the mycobacterial cell wall. Several derivatives of 6,6'-dideoxytrehalose, including N,N'-dialkylamino and 6,6'-bis(sulfonamido) analogs, were prepared and evaluated for antimycobacterial activity against Mycobacterium tuberculosis H(37)Ra and a panel of clinical isolates of Mycobacterium avium. 6,6'-Diaminotrehalose and its diazido precursor were both inactive, but significant activity apparently related to aliphatic chain length was found among the sulfonamides, N-alkylamines, and one of the amidines.
Rose
Jerry D
JD
Southern Research Institute, Drug Discovery Division, 2000 Ninth Avenue South, PO Box 55305, Birmingham, AL 35255-5305, USA.
Maddry
Joseph A
JA
Comber
Robert N
RN
Suling
William J
WJ
Wilson
Larry N
LN
Reynolds
Robert C
RC
D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism*; D003311:Cord Factors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000378:metabolism; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology
D000995:Antitubercular Agents; D003311:Cord Factors; D013449:Sulfonamides; C021099:trehalose monomycolate