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

Matin, Priyanka; Nayeem, S. M. Abdul; Matin, Mohammed Mahbubul; Rahman, Md. Rezaur; Das, Suman; Chakraborty, Dipankar

doi:10.21608/ejchem.2022.133698.5895

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

Document Type : Original Article

Authors

¹ Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong, 4331, Bangladesh

² Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong, Bangladesh

³ Department of Chemical Engineering and Energy Sustainability, Faculty of Engineering, Universiti Malaysia Sarawak, Kota Samarahan, 94300, Malaysia

⁴ Chemical Research Division, Bangladesh Council of Scientific & Industrial Research (BCSIR) Laboratories, Chittagong, 4220, Bangladesh

10.21608/ejchem.2022.133698.5895

Abstract

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 their in 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.

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