Background: Diabetes, a cardiometabolic condition with social and health ramifications, is already a global epidemic. Diabetes affects 422 million people worldwide, with the majority living in middle- and low-income countries, resulting in 1.5 million deaths each year. Inhibiting DPP-IV, an enzyme whose main biological function in diabetes is the breakdown of metabolic hormones like GLP-1, Quassia amara, a plant that contains numerous phytochemicals, has been claimed to be used as a traditional treatment for a variety of metabolic illnesses, as well as having anti-malaria, anti-biotic, anti-diabetes, and anti-anemic characteristics. This work investigated the in-silico inhibitory ability of phytochemicals obtained from Quassia amara against a diabetes-related enzyme, DPP-IV, with the aim of confirming the drug-like potential of ligands from the plant (Quassia amara) in comparison with the standard drug, Alogliptin. Result: As a result of the investigation, five compounds (Vitexin, Quassimarin, Simalikalactone D, Brucein D, and Quassinol) obtained docking scores ranging from − 7.47 to − 6.49 kcal/mol. Conclusion: Many medications have been offered, but the typical side effects have prompted researchers to look for new herbal plants which can be used as permanent treatment with minute side effects. Thus, utilizing computational studies such as molecular docking, molecular mechanics generalized born surface area (MM-GBSA) and the lead compounds' ADMETox characteristics were computed.

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the resistant pathogenic microorganisms that poses a global health threat due to its resistance to β-lactam antibiotics where the protein penicillin-binding protein 2a (PBP2a) plays a crucial role in its resistance. This study explores the potential of phytochemicals from Uvaria chamae, a plant with known medicinal properties, to serve as dual-site inhibitors of PBP2a, targeting both the active and allosteric sites. Methods: Phytochemicals previously identified in U. chamae were subjected to molecular docking and molecular dynamics simulations to evaluate their binding affinities and stability at PBP2a’s active and allosteric sites. The compounds’ pharmacokinetic profiles were predicted in silico using SwissADME tools. Root-mean-square deviation (RMSD), radius of gyration, and binding free energy were analyzed for dynamic stability. Results: Among the evaluated compounds, Uvarinol and Dichamanetin demonstrated high binding affinities compared to the co-crystallized ligand and standard antibiotics like ceftaroline. Uvarinol exhibited the highest binding affinity at both sites, with a docking score of −14.94 kcal/mol and a predicted inhibition constant (Ki) of 0.01 nM. Molecular dynamics simulations further confirmed the robust stability of Uvarinol and Dichamanetin, as indicated by consistently lower RMSD values relative to the co-crystallized ligand. Pharmacokinetic predictions revealed favorable drug-likeness and low toxicity, although Uvarinol showed limited gastrointestinal absorption. Conclusions: Uvarinol and Dichamanetin show promise as dual-site PBP2a inhibitors, offering a novel strategy to combat MRSA resistance. Their structural and pharmacokinetic properties make them viable candidates for further development, though experimental validation and formulation optimization are necessary to overcome bioavailability challenges.

Benign Prostate Cancer (BPC), a prevalent condition predominantly affecting elderly males, manifests with voiding difficulties and urinary retention. A library of compounds from Trigonella foenum-graecum, commonly known as fenugreek was used in this study. We aimed to explore its potential anti-cancer effects by computationally assessing its inhibitory activity on the androgen receptor (AR). For in-silico drug assessment, we employed Maestro 12.8, part of the Schrödinger Suite, to identify the most promising candidates acting as androgen receptor antagonists in the treatment of BPC. Subsequently, 59 fenugreek compounds were retrieved from the PubChem database and subjected to molecular docking against the active site of the target protein, 1E3G. 100-nanosecond molecular dynamics (MD) simulations were performed to assess the stability and compactness of the AR-ligand complexes. Notably, the AR-kaempferol complex exhibited the least fluctuation within the AR active site throughout the simulation trajectory, followed by chlorogenic acid and the reference ligand, hydroxyflutamide. The MM/GBSA values revealed the compounds' maximum free binding energy (-103.3 ± 6, -87.4 ± 23, -68.5 ΔG_bind) for chlorogenic acid, kaempferol, and hydroxyflutamide, respectively. These findings suggest their potential as promising leads for drug development. Further lead optimization and comprehensive studies on the top-ranked ligands identified in this investigation are warranted to advance their potential as therapeutic agents for BPC treatment.Communicated by Ramaswamy H. Sarma.

Spondias mombin is a prominent botanical resource and has garnered recognition within folkloric therapy. Parkinson's disease (PD), characterized by dopaminergic neuron attrition in the substantia nigra, manifests as motor anomalies like tremors, rigidity, and bradykinesia. This study capitalizes on S. mombin's reservoir of 100 characterized phytocompounds and employs computational methodologies to interrogate their potential with 35 PD-associated target proteins. Employing a multifaceted approach, we engaged in molecular docking, ADMET predictions, Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) evaluations, Density Functional Theory (DFT), and Molecular Dynamic Simulations (MDS). This comprehensive framework facilitated insightful structural assessments and predictive analyses. Impressively, flavonoids hailing from S. mombin, including quercetin, catechin, ellagic acid, and epicatechin, showed optimal binding affinities for PD-related target proteins. Moreover, these identified ligands exhibited minimal signs of mutagenicity, tumorigenicity, or irritancy, except for quercetin, which displayed elevated tumorigenic potential. Notably, quercetin and dopamine exhibited varying band gap energies, with quercetin the lowest (3.63 eV) and dopamine the highest (5.76 eV) values. MDS result suggests a synergistic outcome based on the RMSD and RMSF graphs for quercetin highlighting it as the best of all including the co-ligand. In a collective sense, our findings present S. mombin as a promising reservoir of active pharmaceutical ingredients, warranting further exploration for novel PD therapeutic avenues. Consequently, this study underscores the enhanced efficacy of phyto-ligands sourced from S. mombin, advocating their optimization as potential drug candidates.

The target of most cancer chemotherapeutic agents is to drive cancer cells toward death. A fine balance between anti-apoptotic and pro-apoptotic proteins is needed to maintain cellular homeostasis. Any shift favoring the pro-apoptotic ones is needed to drive cellular death in cancer chemotherapy. However, anti-apoptotic proteins such as Bcl-2 and Bcl-xL bind with pro-apoptotic proteins to hinder apoptosis mechanisms. Overexpression of these anti-apoptotic proteins lead to several cancers by preventing apoptosis. In this study, molecular docking, ADMET predictions, and molecular dynamics simulations were performed for the identification of potent inhibitors of anti-apoptotic Bcl-2 with compounds of Morus alba. Our study discovered that Quercetin-3-(6-Malonylglucoside) and Epigallocatechin gallate recorded excellent binding affinity with Bcl-2. Therefore, we conclude that compounds of Morus alba should be subjected to further experimental studies ( in vitro and in vivo) in order to confirm the findings that they could be used as better options in cancer chemotherapy.