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- Diabetes mellitus (DM) is a metabolic condition characterized by chronic hyperglycemia caused by insulin secretion and action deficiencies. Type 2 DM results from impaired insulin secretion by β cells of the pancreas and unresponsive signals between insulin-target tissues and insulin. Most drugs used in treating DM have one or more negative side effects and are primarily focused on lowering blood glucose levels rather than addressing the underlying mechanisms that cause DM. Therefore, developing new drugs to address these underlying causes is a priority. This study seeks to explore the antidiabetic roles of phytochemicals from Chrysobalanus orbicularis Hook. f. (Chrysobalanaceae) using in silico techniques to identify a novel regimen for DM. High-performance liquid chromatography (HPLC) analysis of C. orbicularis identified four bioactive compounds (sapogenin, delphinidin, cyanidin, and petunidin). To screen and find acceptable potential hit compound(s), these compounds were subjected to molecular docking to decipher their interactions with some proteins identified in the literature as being involved in the pathophysiology of DM (dipeptidyl peptidase IV, alpha-amylase, glucagon-like peptide−1 receptor, alpha-glucosidase, poly[ADP-ribose] polymerase 1, and G-protein coupled bile acid receptor 1). Petunidin had the best interaction with most of the proteins based on the precision docking score and MM-PBSA analysis. More importantly, parameters for discovering drugs for biotherapeutic candidates, viz., distribution, absorption, metabolism, toxicity, and excretion, were calculated for petunidin. Our findings suggest that petunidin could be a promising new therapeutic target for treating DM.
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- Malaria remains a significant global health problem; with the potential for developing resistance to conventional antimalarials justifying novel therapeutic approaches. This study investigates the potential of microalgal metabolites as dual-inhibitors of Plasmodium falciparum glutathione S-transferase (PfGST) and apical membrane antigen 1 (AMA1); two of the most important proteins in parasite survival and host cell invasion. By high-throughput molecular docking simulations; we studied binding energy distributions; conformational characteristics by principal component analysis; pharmacophoric and pharmacokinetic research with structure-activity relationships of its inhibitors. Our findings indicate various patterns of interactions: PfGST exhibits a unimodal distribution of binding energy with a maximum at -7.2 kcal/mol; whereas AMA1 exhibits a bimodal distribution with minimum at -6.8 and − 8.3 kcal/mol; suggesting various mechanisms of binding. Specifically; platencin was among the most potent dual-inhibitors with binding energies of -7.30 kcal/mol to PfGST and − 8.20 kcal/mol to AMA1. Pharmacophoric characteristics were found to be the hydrogen-bond acceptors; hydrophobic centers; and aromatic rings as determinants of dual-target activity; the optimal dual-target inhibitory potential occurring with compounds of balanced physicochemical properties. High-resolution molecular interaction mapping validated that while the two targets identify overlapping classes of interactions with the metabolites; PfGST interaction is dominated by hydrophobic contacts and AMA1 exploits higher electrostatic complementarity and hydrogen-bonding networks. ADMET profiling also revealed favorable drug-likeness in dual-inhibitory compounds of intermediate molecular size (420–500 Da) and moderate lipophilicity (LogP 3–6). This study provides a structural basis for rationale design of antimalarial compounds from microalgal metabolites. Our findings confirm the conformational selection hypothesis; in which these compounds selectively bind to and stabilize protein conformations that inhibit parasite function; possibly circumventing known resistance mechanisms.
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