SYNTHESIS AND ANTIFUNGAL ACTIVITIES OF MYRISTIC ACID ANALOGS

Myristic acid analogs that are putative inhibitors of N-myristoyltrans ferase were tested in vitro for activity against yeasts (Saccharomyces cerevisiae, Candida albicans, Cryptococcus neoformans) and filamentou s fungi (Aspergillus niger). Several (+/-)-2-halotetradecanoic acids i ncluding (+/-)-2-bromotetradecanoic acid (14c) exhibited potent activi ty against C. albicans (MIG = 39 mu M), C. neoformans (MIC = 20 mu M), S. cerevisiae (MIC = 10 mu M), and A. niger (MIC < 42 mu M) in RPMI 1 640 media. Improved synthetic methods have been developed for the synt hesis 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.