The human oral cavity harbours a diverse microbial taxon. These microbes, specifically bacteria, metabolise food containing carbohydrates and proteins, but when the oral microbiota health is compromise, this can lead to the formation of dental plaque. Accumulation of plaque and tartar results in gum disease, abscessed tooth, and other oral cavities. Moreso, these bacteria increasingly exhibit multi-drug resistance a major challenge for antimicrobial therapy. Hence, in this study, we identify oral microbes using biochemical test, perform preliminary anti-bacteria efficacy of aqueous extract of Spondias mombin L. fresh bark on the predominant microorganisms found in the human mouth (with oral disease). Techniques used in this study include sample collection from patients with oral disease, the pour-plate cultivation method, and bioassay treatment with S. mombin extracts. In-silico investigation including molecular docking was performed using the AutoDock Vina engine implemented in PyRx. The results obtained from this study indicated Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus sp are potential predominant oral microbes, and S. mombin aqueous extract has inhibitory effects on their growth. The molecular docking of 18 phytocompounds of S. mombin indicated potentially superior binding affinity, in contrast with levofloxacin, the standard. The electronic reactivity and 100 ns dynamic simulation of S. mombin phytocompounds shows oleanolic acid, ellagic acid, rutin, catechin, quercetin, and myricetin atomic-level stability towards fibronectin binding proteins A and B, which are critical for S. aureus adhesion and invasion into the host cell. Overall, these findings support that S. mombin phytocompounds are druggable candidate and require further validation for development in oral disease therapy.
The electronic characteristics and molecular structure of 4,6-dimethyl-2-hydroxy pyrimidine were examined using theoretical and experimental methods. Density functional theory (DFT) at the B3LYP/6-31G(d, p) level was used to determine the optimized molecular geometry and vibrational frequencies, which were then compared to the observed FT-IR spectra. The theoretical and experimental vibrational frequencies were found to be in good agreement. The HOMO and LUMO energies were − 8.96 and − 4.46 eV, respectively, with an energy gap of 4.50 eV, according to frontier molecular orbital analysis, indicating moderate chemical stability. Compared to urea, the computed first-order hyperpolarizability value (1.138 × 10–32 esu) is higher, indicating possible nonlinear optical behavior. Intramolecular charge transfer interactions inside the molecule were verified by a Natural Bond Orbital (NBO) study. Electrophilic and nucleophilic reactive areas were identified using molecular electrostatic potential (MEP) analysis. Additionally, Lipinski’s rule of five drug-likeness evaluation showed that the molecule has advantageous physicochemical characteristics for possible medicinal use.
To optimize Nirmatrelvir as an inhibitor of the MERS-CoV main protease (Mpro), we developed an automated RDKit-based iterative scaffold optimization framework that integrated fragment replacement, combinatorial library enumeration, and chemical feasibility filtering to generate 15,744 drug-like analogs through systematic substitutions at six positions on the Nirmatrelvir scaffold. Structural similarity to Nirmatrelvir was assessed using complementary 2D fingerprint and 3D shape-based analyses of the 15,953 designed analogs and a separate set of 13,090 molecular weight-matched ChEMBL compounds to examine the binding potency in both the modified and randomly selected compound cohorts. Based on the correlation between structural similarity and docking score of the modified molecules, a binding score (BS) approach was advanced to rapidly identify and rank promising lead compounds. Several top candidates exhibited improved binding characteristics compared to that of Nirmatrelvir. To assess the robustness of the BS approach, multiple computational methods were employed, including KDEEP, molecular dynamics (MD) simulations, molecular mechanics/generalized Born surface area (MM/GBSA) free energy calculations, and Boltz-2. The BS ranking showed strong agreement with all computational validation methods, consistently identifying compounds with enhanced binding affinities and stable protein-ligand interactions. The top-ranked compounds, M1, M3, M5, and M6, identified by high Binding Score (BS) values (9.1–10.2), exhibited favorable MM/GBSA binding free energies ranging from − 31.7 to − 42.9 kcal/mol, KDEEP-predicted binding affinities of − 9.5 to − 10.6 kcal/mol, and Boltz-2 predicted pIC₅₀ values of 10.0–11.8. Furthermore, for SARS-CoV-2 Mpro, BS scores also correlated well with available experimental half-maximal inhibitory concentration (IC50) data and Boltz-2 predictions for Nirmatrelvir analogues. Collectively, these findings demonstrate that the BS approach may serve as an efficient strategy for screening, prioritizing, and accelerating the discovery of next-generation coronavirus Mpro inhibitors.
Novel multifunctional medication candidates are needed to treat Alzheimer’s disease (AD), a neurodegenerative illness with few treatments. A nitrogen-containing heterocycle, piperidine, is a popular medicinal chemistry scaffold with broad therapeutic potential. We synthesized a series of novel piperidin-1-yl-phenyl-acetamide derivatives (AS-1 to AS-5) by reacting piperidine with 4-chloroaniline and characterizing them by IR, 1 H NMR, 13 C NMR, and mass spectrometry. All compounds meet Lipinski’s rule of five for drug-likeness and oral bioavailability. AutoDockVina molecular docking demonstrated that compounds AS-5 and AS-2 bind acetylcholinesterase (AChE) with affinities comparable to or higher than donepezil, suggesting they may inhibit AChE. AS-5 was the most potent free radical scavenger in DPPH and FRAP studies. Further behavioral evaluation utilizing Y-maze and Morris water maze tests showed that AS-5 was more effective against Alzheimer’s than AS-1. Piperidin-1-yl-phenyl-acetamide derivatives, particularly the 2,5-dimethyl-substituted counterpart (AS-5), have multifunctional properties due to acetylcholinesterase inhibition and antioxidant activity. These findings suggest AS-5 as a lead chemical for optimizing and developing Alzheimer’s disease treatments. The piperidin-1-yl-phenyl-acetamide derivative (AS-5)’s significant acetylcholinesterase inhibition, robust antioxidant action, and in vivo cognitive enhancement comparable to Donepezil make it important. Structure–activity relationship insight highlights the 2,5-dimethyl substitution as a significant driver of increased anti-Alzheimer action, providing a target for next-generation drug design.
Manganese contamination in drinking water poses a significant environmental and public health concern, particularly in regions impacted by industrial discharges and geogenic leaching. This study investigates the potential of activated biochar derived from Pinus roxburghii pinecones (PCB), an abundant forestry residue, as a sustainable and cost-effective adsorbent for the removal of Mn(II) from aqueous systems. The biochar was chemically activated using potassium hydroxide to enhance its adsorption properties. Comprehensive characterization using Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FTIR) confirmed the development of a highly porous structure and the presence of oxygen-containing functional groups responsible for metal binding. To optimize the adsorption process, Response Surface Methodology (RSM) based on a Box–Behnken Design (BBD) was employed, considering key operational parameters such as pH, adsorbent dosage, stirring speed, and contact time. The optimal conditions were determined to be pH 8.0, adsorbent dosage of 5 g/L, stirring speed of 230 rpm, and contact time of 45.6 min. Under these conditions, a maximum Mn(II) removal efficiency of 83.59
