Synthesis of Protected D-Glucopyranosides as Mucormycosis Inhibitors: DFT, Docking, ADMET, and SAR Studies

Fungal infections especially mucormycosis cause devastating health problems worldwide and the recent invasion of mucormycosis (Mucorales) after SARS-CoV-2 infection worsens the severity of patient conditions leading to increased deaths. Non-ionic sugar esters (SEs) with amphiphilic properties show antimicrobial activities and have potential applications in medicines, foods, agriculture, and pharmaceutical industries. Several benzylidene-protected glucopyranoside esters were synthesized and theirin vitro antifungal potentialities were assessed. With encouraging results against Alternaria alternata their potentialities were checked by molecular docking with three black fungus-related proteins (PDB :ID: 4BFN, 4BFO, and 2WTP) which indicated that the presence of hexanoyl group at the C-2 position of glucopyranoside skeleton highly increased its binding .affinities. Hence, it can be an alternative to azole drugs for the treatment of mucormycosis infections. Molecular orbital, global reactivity descriptors, drug-likeness, and structure -activity relationship are used to rationalize these binding results and to ensure that the compounds are safe for humans.