Structure-based virtual screening of mangiferin derivatives with antidiabetic action: a molecular docking and dynamics study and MPO-based drug-likeness approach

Francisco Flávio da Silva Lopes; Francisco Nithael Melo Lúcio; Matheus Nunes da Rocha; Victor Moreira de Oliveira; Caio Henrique Alexandre Roberto; Márcia Machado Marinho; Emmanuel Silva Marinho; Selene Maia de Morais

doi:10.1007/s13205-024-03978-9

Structure-based virtual screening of mangiferin derivatives with antidiabetic action: a molecular docking and dynamics study and MPO-based drug-likeness approach

3 Biotech. 2024 May;14(5):135. doi: 10.1007/s13205-024-03978-9. Epub 2024 Apr 23.

Authors

Francisco Flávio da Silva Lopes¹, Francisco Nithael Melo Lúcio¹, Matheus Nunes da Rocha², Victor Moreira de Oliveira², Caio Henrique Alexandre Roberto², Márcia Machado Marinho³, Emmanuel Silva Marinho², Selene Maia de Morais^{1

2}

Affiliations

¹ Doctoral Program in Biotechnology, Northeast Biotechnology Network, State University of Ceará, Fortaleza, CE Brazil.
² Postgraduate Program in Natural Sciences, State University of Ceará, Fortaleza, CE Brazil.
³ Science and Technology Centre, Course of Chemistry, State University Vale do Acaraú, Sobral, CE Brazil.

PMID: 38665880
PMCID: PMC11039600 (available on 2025-05-01)
DOI: 10.1007/s13205-024-03978-9

Abstract

Extracts from Mangifera indica leaves and its main component, mangiferin, have proven antidiabetic activity. In this study, mangiferin and its natural derivatives Homomangiferin (HMF), Isomangiferin (IMF), Neomangiferin (NMF), Glucomangiferin (GMF), Mangiferin 6'-gallate (MFG), and Norathyriol (NRT) were compared regarding their action on Diabetes mellitus (DM), employing docking and molecular dynamics (MD) simulations to analyze interactions with the aldose reductase enzyme, the precursor to the conversion of glucose into sorbitol. Notably, HMF showed significant affinity to residues in the active site of the enzyme, including Trp 79, His 110, Trp 111, Phe 122, and Phe 300, with an energy of - 7.2 kcal/mol, observed in the molecular docking simulations. MD reinforced the formation of stable complexes for HMF and MFG with the aldose reductase, with interaction potential energies (IPE) in the order of - 300.812 ± 52 kJ/mol and - 304.812 ± 52 kJ/mol, respectively. The drug-likeness assessment, by multiparameter optimization (MPO), highlighted that HMF and IMF have similarities with polyphenols and glycosidic flavonoids recently patented as antidiabetics, revealing that high polarity (TPSA > 180 Å²) is a favorable property for subcutaneous administration, especially because of the gradual passive cell permeability values in biological tissues, with P_app values estimated at < 10 × 10^-6 cm/s. These compounds are metabolically stable against metabolic enzymes, resulting in a low toxic incidence by metabolic activation, corroborating with a lethal dose (LD₅₀) greater than 2000 mg/kg. In this way, HMF showed a systematic alignment between predicted pharmacokinetics and pharmacodynamics, characterizing it as the most favorable substance for inhibiting aldose reductase.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-03978-9.

Keywords: Antidiabetic; Drug-likeness; Dynamics; Mangiferin derivatives; Molecular docking.

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