Glycine-Conjugated α-Mangostins as Potential Estrogen Receptor Alpha (ERα) Antagonists through Pharmacophore Modeling, Docking Analysis, and Molecular Dynamics Simulations
Source abstract
Abstract
Natural compounds have demonstrated good biological activity when combined with certain amino acids. For example, a glycine-conjugated glycyrrhetinic acid exhibits heightened efficiency against MCF7 cancer cells. Consequently, a molecular modeling analysis is conducted to construct glycine-conjugated α-mangostins and investigate their potential. According to pharmacophore modeling using the ligand-based drug design technique, only two glycine-conjugated α-mangostins conform to the pharmacophore features. The docking simulation results show that the Am1Gly conjugate can interact with the estrogen receptor-α (ERα) with a binding energy of −10.91 kcal/mol. This interaction is further supported by molecular dynamics simulations performed over a 200 ns timeframe. Based on molecular dynamics modeling using the MMPBSA method, the binding affinity of Am1Gly (ΔGTotal = −48.79 kcal/mol) is determined. The results of this analysis indicate that Am1Gly might function as an antagonist to estrogen receptors.
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Research context
OpenAlex topics: Bioactive Compounds and Antitumor Agents · Synthesis and biological activity · Natural product bioactivities and synthesis
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jln. Raya Bandung Sumedang KM. 21, Jatinangor 45363, West Java, Indonesia
Department of Pharmacochemistry, Faculty of Pharmacy, Universitas Mulawarman, Jl. Muara Muntai, Gn. Kelua, Samarinda 75242, East Kalimantan, Indonesia
Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jln. Raya Bandung Sumedang KM. 21, Jatinangor 45363, West Java, Indonesia
Research Collaboration Centre for Radiopharmaceuticals Theranostic, BRIN, Jln. Raya Bandung Sumedang KM. 21, Jatinangor 45363, West Java, Indonesia
Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia
Funding
Doctoral Research Grant of The Ministry of Education, Culture, Research, and Technology Indonesia
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