Expansion of the antifungal activities through in silico docking study of compounds from Albizia lebbeck fruits

Abstract

The development of new computational and experimental techniques that are efficient, fast, and accurate has become a priority for researchers in all domains around the world. The present manuscript deals with the computational investigation of quercitrin (1), lebbeckisoetin A (2), quercetin-3-O-_β_-D-glucopyranoside (3), (_E_)-_p_-coumaric acid (4), eugenol (5), eugenol, 1-acetate (6), chiakine (7), hexancosan-1',26'-dioate of bis[(2_S_), 2,3-dihydroxypropyl] (8), oleanolic acid (9), betulin (10), hopan-29-ol (11), hopan-30-ol (12), 22-hydroxyhopan-3-ol (13), and lupeol (14). These compounds were all isolated from the fruit of _Albizia lebbeck_. Only lebbeckisoetin A (2) and chiakine (7) were previously evaluated for their experimental antimicrobial activities, which both revealed potent antifungal activities. This theoretical study was undertaken in the framework of better understanding the experimental results at the atomic level and to expand the antimicrobial assays of the other non-tested compounds. The virtual screening of the antimicrobial activity was performed on Maestro Schrӧdinger 4.2.1 software using the crystal structures of sterol 14-alpha demethylase (CYP51) from _Candida albicans_ in complex with the tetrazole-based antifungal drug candidate VT1161 (VT1) (PDB Id: 5TZ1) and the crystal structure of sterol 14-alpha demethylase (CYP51) from the pathogenic yeast _Candida albicans_ in complex with the antifungal drug posaconazole (PDB Id: 5FSA). This is the first docking study of natural compounds using these 5TZ1 and 5FSA as proteins. Compounds (1-10) reveal interesting binding strength with both 5TZ1 and 5FSA proteins, with a docking score ranging from -7.892 to -5.256, supporting the experimental results. In addition, compounds (1-9) were mostly active due to the formation of π-π interactions, H-bonds, and hydrophobic interactions, as well as π-cation and salt bridge interactions, with both 5TZ1 and 5FSA.