Total synthesis and in vitro-antifungal activity of (+/-)-2-methoxytetradecanoic Acid.
The marine fatty acid (+/-)-2-methoxytetradecanoic acid was synthesized in two steps (71% overall yield) starting from commercially available methyl-2-hydroxy-tetradecanoate. The title compound was antifungal against Candida albicans (ATCC 14053) in RPMI medium and Aspergillus niger (ATCC 16404) and Cryptococcus neoformans (ATCC 66031) in SDB medium at the minimum inhibitory concentration (MIC) of 100 mM, which compares to the fungitoxicity of a 2-iodotetradecanoic acid against the same fungi. The title compound was also five to ten times more cytotoxic than capric acid to C. albicans and A. niger in the tested medium but comparable in cytotoxicity to either capric acid and its 2-methoxylated analog to C. neoformans. The antifungal activity of (+/-)-2-methoxytetradecanoic acid is explained in terms of inhibition of N-myristoyltransferase.
Carballeira
Néstor M
NM
Department of Chemistry, University of Puerto Rico, San Juan, Puerto Rico. ncarball@upracd.upr.clu.edu
Ortiz
Denisse
D
Parang
Keykavous
K
Sardari
Soroush
S
D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000493:pharmacokinetics; D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001234:Aspergillus niger / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D003455:Cryptococcus neoformans / Q000187:drug effects; D005227:Fatty Acids / Q000138:chemical synthesis; D066298:In Vitro Techniques; D009226:Myristates / Q000138:chemical synthesis* / Q000494:pharmacology*; D009227:Myristic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*
C486638:2-methoxytetradecanoic acid; D000935:Antifungal Agents; D005227:Fatty Acids; D009226:Myristates; D009227:Myristic Acids; D000666:Amphotericin B; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase