Evaluation of Compounds from Balanites aegyptiaca against Squalene Epoxidase of Micropsorum gypseum—In Vitro and In Silico Studies

Abstract

Microsporum gypseum is a dermatophyte with a geophilic nature that is found all over the globe. It mainly causes tinea in the scalp, arms, and legs in humans. Squalene epoxidase (SE) is a crucial enzyme in M. gypseum for the biosynthesis of ergosterol. The medicinal plant Balanites aegyptiaca is an abundant supply of secondary constituents with great therapeutic values. In this research, the fruit epicarp portion was used to inhibit M. gypseum using experimental and computational techniques. The anti-dermatophytic activity of epicarp extracts on M. gypseum was evaluated using the poison plate method at five different concentrations. At 3 mg/mL, the M. gypseum was completely controlled by the fractioned chloroform extract of epicarp. The compounds from previous research were utilized for docking studies (Abuthakir et al., 2022). The ideal compounds and the drug terbinafine were then docked using Schrödinger’s Glide module. It demonstrates that (3E)-7-Hydroxy-3,7-dimethyl-3-octen-1-yl-6-O-(6-deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranoside outperforms other substances and the drug terbinafine in docking analysis. Desmond, Schrödinger Molecular Dynamics simulations were also performed for (3E)-7-Hydroxy-3,7-dimethyl-3-octen-1-yl-6-O-(6-deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranoside-squalene epoxidase complexes. The complex appears to be more stable, according to the MD simulation research. This study indicates that (3E)-7-Hydroxy-3,7-dimethyl-3-octen-1-yl-6-O-(6-deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranoside could be used as a potential inhibitor of M. gypseum growth, and it could be studied further.

Anti-Infection of Oral Microorganisms from Herbal Medicine of Piper crocatum Ruiz & Pav

“…A new class of synthetic antimycotics referred to as allylamines are identified by their capacity to function as squalene epoxidase inhibitors. [51][52][53] Naftifine serves as an exemplar of an allylamine antifungal and was the first substance discovered in 1974, during routine research, to possess antifungal properties. Naftifine's potent antifungal activity both in vitro and in vivo led to its clinical development as a topical antimycotic.…”

“…Allylamine antifungals work akin to azoles, but they act earlier on the ergosterol production pathway. 53,55,56 They impede squalene epoxidase, an enzyme responsible for converting squalene to ergosterol, therefore disrupting the development of the fungal cell wall. 57 Semisynthetic cyclic lipopeptides known as echinocandins prevent cell wall formation by non-competitive inhibition of the (1,3)-β-D-glucan synthase complex, as shown in Figure 5.…”

“…Allylamine antifungals work akin to azoles, but they act earlier on the ergosterol production pathway. 53 , 55 , 56 They impede squalene epoxidase, an enzyme responsible for converting squalene to ergosterol, therefore disrupting the development of the fungal cell wall. 57 …”