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

Nevine H Hassan; Seham S El-Hawary; Mahmoud Emam; Mohamed A Rabeh; Usama Ramadan Abdelmohsen; Nabil M Selim

doi:10.1021/acsomega.2c00063

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

ACS Omega. 2022 Apr 13;7(16):13808-13817. doi: 10.1021/acsomega.2c00063. eCollection 2022 Apr 26.

Authors

Nevine H Hassan¹, Seham S El-Hawary², Mahmoud Emam³, Mohamed A Rabeh^{1

2}, Usama Ramadan Abdelmohsen^{4

5}, Nabil M Selim²

Affiliations

¹ Pharmacognosy Department, Faculty of Pharmacy, Modern University for Technology and Information, Cairo 11571, Egypt.
² Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Giza 11562, Egypt.
³ Phytochemistry and Plant Systematics Department, National Research Centre, Dokki, Cairo 12622, Egypt.
⁴ Pharmacognosy Department, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt.
⁵ Pharmacognosy Department, Faculty of Pharmacy, Deraya University, 61111 New Minia, Egypt.

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 IC₅₀ value of 12.23 μg/mL. Our results highlighted the antifungal potential of Nephthea sp. metabolites.