COMPARATIVE IN SILICO ANALYSIS OF BIOACTIVE COMPOUNDSFROM OCIMUM GRATISSIMUM, LAURUS NOBILIS, CYMBOGONCITRATUS PIPERER GUINEENSE, AND PSIDIUM GUAJAVAFORPOTENTIAL ANTILIPIDEMIC ACTIVITY
Faculty
Department
Year of Publication
Keyword
upload
Publication Type
Abstract
Hyperlipidemia is a major risk factor for atherosclerotic cardiovascular disease(ASCVD), necessitating multi-target therapeutic strategies to counter excessivecholesterol synthesis, absorption, and poor triglyceride clearance (Ray et al., 2023). Given the side effects and limitations of synthetic lipid-lowering drugs, this in silicostudy evaluated phytochemicals from five Nigerian plants (Ocimumgratissimum, Laurus nobilis, Cymbopogon citratus, Piper guineense, and Psidiumguajava) as
natural antilipidemic agents. Molecular docking assessed the binding affinity ($\DeltaG$) of over 100 compounds against five key targets of lipid metabolism: 3-Hydroxy- 3-methylglutaryl-coenzyme A Reductase (HMG-CoA Reductase, PDB ID1HWK), Peroxisome Proliferator-Activated Receptor Gamma (PPAR-$\gamma$, PDBID6ENQ), PPAR-$\delta$ (PDB ID 7WGN), Hydroxycarboxylic Acid Receptor 2(HM7A4, PDB ID 8K5B), and Niemann-Pick C1-Like 1 (NPC1L1, PDBID7DFZ). Promising hits demonstrating superior binding to established clinical standards werethen subjected to ADMET (Absorption, Distribution, Metabolism, Excretion, andToxicity) profiling to predict their pharmacokinetic and safety profiles. The screeningidentified several compounds displaying significantly stronger binding affinities thantheir respective clinical standards. Notably, the Laurus nobilis constituent, CID91274708, showed unparalleled affinity for PPAR-$\delta$ (-8.57 kcal/mol), substantially surpassing the Pemafibrate standard (-7.16 kcal/mol). The potent HMG- CoA Reductase inhibitor, CID 165359504, also demonstrated robust binding (-7.86kcal/mol) against the Atorvastatin standard (-5.40 kcal/mol), suggesting a novel poly- glycosidic scaffold for inhibition. Furthermore, the NPC1L1 inhibitor, CID72
viii
(Psidium guajava), showed enhanced binding (-5.18 kcal/mol) comparedtoEzetimibe (-4.51 kcal/mol). ADMET analysis confirmed that the prioritizedcompounds, notably CID 91274708 and CID 72, possessed ideal pharmacokineticprofiles, while successfully filtering out candidates with high predicted toxicological risks, such as the genotoxic CID 6037 (Mohamed et al., 2024). The results validatethe potential of compounds from Nigerian medicinal plants as structurally diverse, high-affinity leads for multi-target antilipidemic therapy, providing a computational basis for future in vitro and in vivo studies aimed at drug discovery (Yadav et al., 2021).
natural antilipidemic agents. Molecular docking assessed the binding affinity ($\DeltaG$) of over 100 compounds against five key targets of lipid metabolism: 3-Hydroxy- 3-methylglutaryl-coenzyme A Reductase (HMG-CoA Reductase, PDB ID1HWK), Peroxisome Proliferator-Activated Receptor Gamma (PPAR-$\gamma$, PDBID6ENQ), PPAR-$\delta$ (PDB ID 7WGN), Hydroxycarboxylic Acid Receptor 2(HM7A4, PDB ID 8K5B), and Niemann-Pick C1-Like 1 (NPC1L1, PDBID7DFZ). Promising hits demonstrating superior binding to established clinical standards werethen subjected to ADMET (Absorption, Distribution, Metabolism, Excretion, andToxicity) profiling to predict their pharmacokinetic and safety profiles. The screeningidentified several compounds displaying significantly stronger binding affinities thantheir respective clinical standards. Notably, the Laurus nobilis constituent, CID91274708, showed unparalleled affinity for PPAR-$\delta$ (-8.57 kcal/mol), substantially surpassing the Pemafibrate standard (-7.16 kcal/mol). The potent HMG- CoA Reductase inhibitor, CID 165359504, also demonstrated robust binding (-7.86kcal/mol) against the Atorvastatin standard (-5.40 kcal/mol), suggesting a novel poly- glycosidic scaffold for inhibition. Furthermore, the NPC1L1 inhibitor, CID72
viii
(Psidium guajava), showed enhanced binding (-5.18 kcal/mol) comparedtoEzetimibe (-4.51 kcal/mol). ADMET analysis confirmed that the prioritizedcompounds, notably CID 91274708 and CID 72, possessed ideal pharmacokineticprofiles, while successfully filtering out candidates with high predicted toxicological risks, such as the genotoxic CID 6037 (Mohamed et al., 2024). The results validatethe potential of compounds from Nigerian medicinal plants as structurally diverse, high-affinity leads for multi-target antilipidemic therapy, providing a computational basis for future in vitro and in vivo studies aimed at drug discovery (Yadav et al., 2021).
Supervisor(s)
co-supervisor