Please use this identifier to cite or link to this item: https://www.um.edu.mt/library/oar/handle/123456789/116341
Title: Identification of potential novel clinical applications for Maltanedienol using a structure-based drug design approach
Authors: Fitzgerald, Martina (2023)
Keywords: Maltanedienol
Ligands
Crystallography
Marine algae -- Mediterranean Region
Dietary supplements industry
Issue Date: 2023
Citation: Fitzgerald, M. (2023). Identification of potential novel clinical applications for Maltanedienol using a structure-based drug design approach (Master's dissertation).
Abstract: Gutierrez et al., obtained a patent for Maltanedienol, an extract of Padina pavonica, in 1992 for its calcium fixation ability in mammals. Since its discovery, the macroalgae’s active principle, Maltanedienol, has been studied by multiple researchers for its efforts in positive bone turnover, being present on the Maltese market as a food supplement for post-menopausal osteoporosis and osteopenia. A knowledge gap is presented, since there is no information regarding the potential clinical use of Maltanedienol which is not related to calcium fixation and positive bone turnover. Therefore, the aim of this study is to identify novel clinical targets for Maltanedienol unrelated to its calcium fixing ability. Conformational analysis was performed on Maltanedienol at each of 20 targets unrelated to calcium fixation identified by D’Emanuele in 2019 found to be crystallographically resolved on the Protein Data Bank®. For each target, the optimal conformer was chosen and the 4 targets having the highest affinity for Maltanedienol were selected for further evaluation. These targets were Aldo Keto Reductase Family 1 Member B10, Nuclear Receptor ROR-Gamma, Oxysterols Receptor LXR-Beta and ALK Tyrosine Kinase Receptor. Two-dimensional topology maps were generated for each of the 4 Maltanedienol target complexes to identify the critical interactions forged between them. Seed fragments were modelled, and de novo growth was allowed within each target ligand binding pocket at sites on the Maltanedienol scaffold which are not critical to binding. Novel analogs of Maltanedienol were created, for which calculation of physicochemical characteristics and predicted oral toxicity was carried out. This study contributes to the existing body of knowledge through the identification of 4 high affinity targets for Maltanedienol whose biological function is unrelated to calcium fixation.
Description: M.Pharm.(Melit.)
URI: https://www.um.edu.mt/library/oar/handle/123456789/116341
Appears in Collections:Dissertations - FacM&S - 2023
Dissertations - FacM&SPha - 2023

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