Semisynthesis of Myristic Acid Derivatives and their Biological Activities: A Critical Insight
Abstract
Abstract Naturally occurring chemical substances and their semisynthetic derivatives have shown various biological activities. In this context, Myristic acid, a naturally occurring saturated fatty acid found in nutmeg and has shown diverse biological actions against fungi, viruses, cancerous cells, and parasitic microbes. Several semisynthetic derivatives of myristic acid such as esters, amides, and hydrazones are reported to possess a wide spectrum of biological activities especially inhibition of N-myristoyltransferase (NMT) which is necessary for the biological function of the cellular and viral proteins in the malignant transformation of cancerous cells. The analogs, 2-hydroxymyristoyl-CoA, 2-bromomyristoyl-CoA, 2-fluoromyristoyl-CoA have shown competitive inhibition of NMT at K i =45, 450, 200 nM, respectively. The 11-oxatetradecanoic acid inhibited >99% of cultured trypanosomes within 24 h. The 3-fluoro-13-oxatetradecanoic acid effective against HIV-1 production (ID50 = 1-5 μM). The 2-bromo tetradecanoic acid had the most potent antifungal activities against Saccharomyces cerevisiae (MIC = 10 μM), Candida albicans (MIC = 39 μM), Cryptococcus neoformans (MIC = 20 μM) and Aspergillus niger (MIC < 42 μM) in RPMI 1640 media, respectively. However, 4-oxa tetradecanoic acid and 9-oxatetradecanoic acid were found to be active against Cryptococcus neoformans (MIC=30 μM)) and moderately effective against Saccharomyces cerevisiae (MIC=50 μM). This review highlights the Nutmeg and its contents, chemistry of myristic, semisynthetic modification of myristic acid, and their biological activities.