Rational design, synthesis, analysis and antifungal activity of novel myristic acid derivatives as N-myristoyltransferase inhibitors

Abstract

A demand for the discovery of new antifungal agents has rose significantly because of a rise in morbidity and related mortality due to systemic fungal infections. N-myristoyltransferase (NMT) has been recognized as a new target for the treatment of fungi infections in recent years. Herein, we report a new series of myristic acid derivatives as antifungal agents by inhibiting N-myristoyltransferase (NMT). The myristic acid derivatives were rationally designed by targeting NMT via docking studies and ADMET studies. The designed myristic acid derivatives were prepared by converting myristic acid to acid chloride followed by coupling with aryl amines to yield the title compounds. The synthesized compounds were purified and analyzed by IR, NMR and Mass spectral analysis. Thereafter, we perform the target NMT inhibition assay. In NMT inhibition assay results, the compound 3g (IC50 = 0.931 μM) had superior activity than other myristic acid derivatives and myristic acid (IC50 = 4.213 μM). In vitro antifungal screening activity results, the compound 3g was more active against Candida albicans (MIC50 =10.94 μg mL−1) than fluconazole (MIC50 = 17.76 μg mL−1). In case of Aspergillus niger (A. nig) strain, compound 3b (MIC50 =13.17 μg mL−1) shows better activity than fluconazole (MIC50 =16.30 μg mL−1). The illustration about the design, synthesis, analysis, and evaluation of myristic acid derivatives is reported.