Synthesis and antifungal activities of myristic acid analogs.
Myristic acid analogs that are putative inhibitors of N-myristoyl-transferase were tested in vitro for activity against yeasts (Saccharomyces cerevisiae, Candida albicans, Cryptococcus neoformans) and filamentous fungi (Aspergillus niger). Several (+/-)-2-halotetradecanoic acids including (+/-)-2-bromotetradecanoic acid (14c) exhibited potent activity against C. albicans (MIC = 39 microM), C. neoformans (MIC = 20 microM), S. cerevisiae (MIC = 10 microM), and A. niger (MIC < 42 microM) in RPMI 1640 media. Improved synthetic methods have been developed for the synthesis of 12-fluorododecanoic acid (12a) and 12-chlorododecanoic acid (12c). Three novel fatty acids, 12-chloro-4-oxadodecanoic acid (8a), 12-phenoxydodecanoic acid (12i), and 11-(4-iodophenoxy)-undecanoic acid (13d) were also synthesized and tested.
Parang
K
K
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Knaus
E E
EE
Wiebe
L I
LI
Sardari
S
S
Daneshtalab
M
M
Csizmadia
F
F
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects*; D006801:Humans; D007624:KB Cells; D008826:Microbial Sensitivity Tests; D009227:Myristic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D000970:Antineoplastic Agents; D009227:Myristic Acids