Potential Inhibitors of CYP51 Enzyme in Dermatophytes by Red Sea Soft Coral Nephthea sp.: In Silico and Molecular Networking Studies

Abstract

In this study, the n-hexane fraction of soft coral Nephthea sp. gathered from the Red Sea was evaluated for its antidermatophyte activity. The antidermatophyte activity was performed versus different fungi, including Microsporum canis, Trichophyton gypseum, and Microsporum mentagrophytes, using a broth microdilution method. The n-hexane fraction showed minimum inhibitory concentrations (MICs) against the tested dermatophytes of 104.2 ± 20.8, 125 ± 0.0, and 83.33 ± 20.83 μg/mL respectively. The chemical constitution of the lipoidal matter (n-hexane fraction) was characterized by gas chromatography coupled with a mass spectrometer (GC-MS). The unsaponifiable fraction (USAP) of Nephthea sp. showed relative percentages of hydrocarbons and vitamins of 69.61% and 3.26%, respectively. Moreover, the percentages of saturated and unsaturated fatty acids were 53.67% and 42.05%, respectively. In addition, a molecular networking study (MN) of the GC-MS analysis performed using the Global Natural Products Social Molecular Networking (GNPS) platform was described. The molecular docking study illustrated that the highest binding energy score for spathulenol toward the CYP51 enzyme was -8.3674 kcal/mol, which predicted the mode of action of the antifungal activity, and then the results were confirmed by the inhibitory effect of Nephthea sp. against CYP51 with an IC50value of 12.23 μg/mL. Our results highlighted the antifungal potential of Nephthea sp. metabolites.