Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management.

Molecular docking is a computational technique that predicts the binding affinity of ligands to receptor proteins. Although it has potential uses in nutraceutical research, it has developed into a formidable tool for drug development. Bioactive substances called nutraceuticals are present in food sources and can be used in the management of diseases. Finding their molecular targets can help in the creation of disease-specific new therapies. The purpose of this review was to explore molecular docking's application to the study of dietary supplements and disease management. First, an overview of the fundamentals of molecular docking and the various software tools available for docking was presented. The limitations and difficulties of using molecular docking in nutraceutical research are also covered, including the reliability of scoring functions and the requirement for experimental validation. Additionally, there was a focus on the identification of molecular targets for nutraceuticals in numerous disease models, including those for sickle cell disease, cancer, cardiovascular, gut, reproductive, and neurodegenerative disorders. We further highlighted biochemistry pathways and models from recent studies that have revealed molecular mechanisms to pinpoint new nutraceuticals' effects on disease pathogenesis. It is convincingly true that molecular docking is a useful tool for identifying the molecular targets of nutraceuticals in the management of diseases. It may offer information about how nutraceuticals work and support the creation of new therapeutics. Therefore, molecular docking has a bright future in nutraceutical research and has a lot of potentials to lead to the creation of brand-new medicines for the treatment of disease.

Secondary structure peptide mimetics: design, synthesis, and evaluation of beta-strand mimetic thrombin inhibitors.

Constrained dipeptide mimetic templates were designed to mimic the secondary structure of peptides in a beta-strand conformation. Two templates corresponding to the D-Phe-Pro portion of the thrombin inhibitor D-Phe-Pro-ArgCH2Cl were synthesized and converted into nine alpha-ketoamide and alpha-ketoheterocycle inhibitors of thrombin. Additionally, a template corresponding to L-Phe-Pro was synthesized and converted to a thrombin inhibitor. The in vitro inhibition of thrombin by these compounds was determined, and those corresponding to the D-Phe-Pro were found to be more potent inhibitors than the L-Phe-Pro mimetic. The alpha-ketoamides were found to be more potent than the alpha-ketoheterocycles but had much slower on rates. By comparison of a series of alpha-ketoamide analogues, it is apparent that the there is a preference for binding of bulky hydrophobic substituents in the P' portion of the thrombin active site. Three of the inhibitors (MOL098, MOL144, and MOL174) were screened against a series of coagulation and anticoagulation enzymes and found to be selective for inhibition of the coagulation enzymes. Two of the inhibitors were tested in in vitro models of intestinal absorption and found to have low absorption potential. The compounds were then tested in vivo in both rats and primates, and one of them (MOL144) was approximately 25% absorbed in both species. This study has delineated the synthesis of constrained dipeptide beta-strand mimetics and validated the potential for compounds of this type as potent thrombin inhibitors and possible drug leads.

Highly efficient and versatile synthesis of libraries of constrained beta-strand mimetics.

The general approach of using a bicyclic template to produce inhibitors of the protease superfamily of enzymes has been investigated. The Diels Alder cycloaddition reaction on solid support has been found to be highly efficient for the synthesis of libraries of compounds that mimic the beta-strand secondary structure of proteins. Several potent and selective inhibitors of proteases have been discovered.