Methyl α-D-glucopyranoside (MDGP), a naturally occurring derivative of carbohydrates, is of interest to medicinal chemists because of its potential medical applications, especially as an antibacterial and antifungal agent. Gaussian 09 and density functional theory (DFT) were utilized to produce chemical descriptors for this investigation. The prediction of activity spectra for substances (PASS) has yielded preliminary data regarding the antifungal, antibacterial, antiviral, and anticancer properties of these compounds. Compared to bacterial species, fungal species scored higher on the PASS-predicted pathogens. We used web tools and an internet database to calculate the absorption, distribution, metabolism, and excretion (ADME) and toxicity of MDGP and its derivatives to assess their safe application and forecast their clinical phases as therapeutic molecules. Molecular docking was used to identify viable therapeutic options for microbial infections by first validating the biological importance of bacterial and fungal proteins. Molecular docking analysis demonstrated the encouraging binding affinity of C2 for both proteins (-6.2 kcal/mol against 5V8E and -5.9 kcal/mol against 7BLY). Ultimately, based on their structural side chain in the D-glucopyranoside sequence, these particular derivatives are found to have greater antibacterial potential than antifungal potential.

1,2,3,4-Tetrahydro-pyrimidine-5-carbonitrile derivatives were synthesized (compounds 1a-d) by the Biginelli reaction of substituted aromatic aldehydes, cyano-ethyl acetate, and urea/thiourea in absolute ethanol. In the next step, acid compounds (2a-d) were formed via the hydrolysis of nitrile group using sulfuric acid (70%), and condensed with the appropriated amino phenol to give the corresponding N-Aryl-1, 2, 3, 4-tetrahydropyrimidine-5-carboxamide derivatives (3a-d). FTIR, 1H-NMR, and 13C-NMR were used to verify the structures of the discovered compounds. All of these novel compounds yielded spectroscopic evidence consistent with their suggested structures. Compounds having strong anti-fungal action against Candida neoformans (ATCC 208881, H99 Type strain) and Candida albicans (ATCC 90028, CLSI reference) were found by the Communities for Antimicrobial Drug Development in Australia.

Novel antimicrobial and antifungal medicines are desperately needed, as evidenced by the increase in antibiotic resistance and other fungal diseases. Previously, we designed methyl α-D-glucopyranoside derivatives (2–8), which are essential for bacterial and fungal replication, in the context of ferulic acid decarboxylase inhibitors. The compounds tri-O-acyl and tri-O-p-bromophenyl derivatives were developed via the selective acylation of glucopyranoside. The compounds containing glucopyranoside derivatives showed remarkable antibacterial and antifungal efficacy when tested in silico against bacteria and fungi via PASS prediction. The compounds showed less toxicity, according to the cytotoxicity assessment. To clarify the mode of action, binding energies, and interaction characteristics of the synthesized compounds that target ferulic acid decarboxylase, extensive molecular docking experiments were conducted. To assess the absorption, distribution, metabolism, and toxicity of these substances, pharmacokinetic predictions were performed. The combination of pharmacokinetic and drug-likeness predictions has shown encouraging results. To summarize, the potential of these derivatives as candidates for the creation of novel antimicrobial drugs that target ferulic acid decarboxylase is highlighted by an integrated computational method that combines molecular docking, molecular dynamics simulation (MDS), ADMET assessment, and density functional theory (DFT) calculations.

In the present scenario of eco-preservation and eco-safe utilization, researchers globally have been attracted to the utilization of raw and sustainable products having significant therapeutic potential that allow safety, modality, and biological activeness with environmental compatibility. Ar-turmerone has various pharmacological actions, including antidepressant, antiepileptic, anti-dermatophyte, antivenom, anticancer, antiplatelet activity, etc. In the present work, we investigated Ar-Turmerone (Ar-Tume), one of the chief phytoconstituents present in Curcuma longa for human anticholinesterase (AChE) inhibitor (4PQE) and human salivary alpha-Amylase dimer (1XV8) hydrolase inhibitor as a natural product-based emerging scaffold. Our study reveals that the selected compound Ar-Tume showed remarked biological, ADMET profiling, and superior docking scores/negative binding energies (-7.9 against 4PQE and -6.7 against 1XV8) concerning the reference drugs, which attributed to the strong hydrogen-bonding interactions both towards both anti-Alzheimers and antidiabetic capabilities.

Employing computer-aided drug design techniques, the physicochemical, biological, and pharmacokinetic properties of several derivatives of methyl α-D-mannopyranoside were explored. Geometrical optimization was conducted using density functional theory (DFT) with a 3-21G basis set, yielding crucial insights into the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). From these data, softness, electron affinity, ionization potential, electronegativity, hardness, electrophilicity, and chemical potential were derived. Notably, compound 1 (mannopyranoside) exhibited the widest energy gap (0.27439 eV), while compound 4 (lauryl derivatives) displayed the narrowest energy gap (0.01924 eV). Furthermore, comprehensive studies encompassing geometrical, thermodynamic, molecular orbital, and electrostatic potential analyses were conducted to elucidate the physical and chemical behavior of the compounds. Molecular docking against the Smallpox virus (PDB 3IGC) proteins enabled the investigation of binding affinity, mode, and interactions with the receptor. ADMET prediction was employed to compare the absorption, distribution, metabolism, and toxicity of the compounds, revealing that compound 6 (a palmitoyl derivative) has the highest free energy and internal energy. A 100 ns molecular dynamics (MD) simulation was used to observe the complex structure formed by the 3IGC protein under in silico physiological conditions to determine its stability over time. It showed a stable conformation and binding pattern in a stimulating mannopyranoside derivative environment. Overall, this study provides valuable insights into the biochemical impact of these compounds on the environment and the human body, offering significant implications for future research endeavors. These findings suggest promising prospects for the development of effective antiviral agents targeting smallpox.

Introduction: The 5-HT1B receptor has a potential role in various psychiatric disorders such as depression, anxiety, and post-traumatic stress disorder. The objective of this study was to perform docking and molecular dynamics simulation to evaluate at atomic level the behavior of N, N-dimethyltryptamine (DMT) on 5-HT1B receptor. Methods: In this study, initially, a search for DMT was performed using the PubChem database. Subsequently, molecular docking was executed using AutoDock Vina based in PyRx 0. 8 with a 95% analogy. Additionally, ergotamine (ERG) and serotonin were used as control. Then, it ran a total of 100 ns molecular dynamics simulations on 5-HT1B bound with DMT, serotonin, 112814775, and ERG. Finally, pharmacokinetic prediction and IV acute toxicity for analogues and DMT were performed. Results: It was possible to show that 112814775 had the lowest binding energy with the receptor. In addition, 112814775 presented great conformational stability, low mobility, and stiffness compared to the control ligands: ERG, serotonin, and DMT subsequent dynamic analysis. With respect to the free energy calculation, contributions such as Van der Waals, electrostatics, and nonpolar interactions for all systems, were highlighted. Conclusion: 112814775 showed affinities with 5-HT1B receptor and evidenced notable behavior by molecular dynamic simulation according to root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), solvent-accessible surface area (SASA), the radius of gyration, number of hydrogen bond, and free energy calculated. These results established the possible relevance of in-silico studies in search of DMT analogues against the 5-HT1B receptor, which may be associated with alterations such as depression and anxiety, and may become future study molecules for the treatment of this type of disorder.

Introduction: Aldehyde dehydrogenase 1A1 (ALDH1A1) is an enzyme involved in cellular detoxification and plays an important role in maintaining cancer stem cells and chemoresistance. This study explores the potential of four theophylline derivatives (compounds A, B, C, and D) as ALDH1A1 inhibitors using molecular docking, ADME analysis, toxicity predictions, and molecular dynamics simulations. Materials and Methods: Four compounds were chosen based on their strong experimental and predicted biological activities. Docking with human ALDH1A1 was performed using AutoDock Vina (v1.1.2), while ADMET properties were assessed with ADMETlab 3.0 and ProTox 3.0. Molecular dynamics simulations were carried out with GROMACS 2024.2 to evaluate the dynamic behavior and binding stability of the complexes. Results: Molecule A showed the highest binding affinity (–11.3 kcal/mol) and established substantial interactions with important residues such as TRP178, TYR297, and PHE171. ADMET analysis indicated that compounds A and C have high intestinal permeability, and all compounds displayed low toxicity risks, supporting their promise as therapeutic candidates. Molecular dynamics simulations confirmed that ALDH1A1’s overall structure remains stable during the simulation and revealed strong hydrogen bonding in complex A, as supported by favorable RMSD, SASA, and RMSF values. Conclusions: The integrated approach combining molecular docking, ADMET analysis, and molecular dynamics simulations confirms that Molecule A is the most promising ALDH1A1 inhibitor, exhibiting stable binding, favourable pharmacokinetic properties, and robust interactions with several residues. These results provide a strong foundation for further experimental validation and optimization in the development of targeted cancer therapies.

Rynchotechum ellipticum has shown promising neuropharmacological potential, particularly owing to its antioxidant and neuroprotective properties. Preliminary studies have suggested that its bioactive compounds may modulate neurotransmitter systems and help mitigate neurodegenerative processes, making it a candidate for further neurological research. To pinpoint the phytocompounds responsible for the neuropharmacological activity, a detailed docking study was performed on the phytocompounds of R. ellipticum using GABA protein as the molecular target. Among the studied compounds, stigmasterol exhibited the highest docking score (6.727 kcal/mol), suggesting a strong binding affinity for the GABA receptor. Notably, the terminal phenolic group of stigmasterol formed a hydrogen bond with Asp192. This interaction is significant, as hydrogen bonds often contribute to the specificity and strength of ligand-receptor interactions. In addition to hydrogen bonding with Asp192, stigmasterol also engages in van der Waals interactions with various residues surrounding its binding site. These residues include Arg194, Ser195, Trp196, Asn60, Tyr58, Val203, Gln204, Ser205, Ser206, Thr207, Tyr210, Val212, Ala161, Tyr160, Ser159, Gly158, Lys156, and Pro140. The presence of multiple van der Waals interactions suggests a stable binding conformation, which may enhance the pharmacological effects of stigmasterol. Complex network of hydrogen bonds, hydrophobic interactions, ionic interactions, and water-mediated bonds works synergistically to stabilize stigmasterol within the GABA receptor, ensuring a promising binding that is essential for the receptor’s sedative effect. From present analysis, we conclude that stigmasterol may be responsible for the pharmacological activity of R. ellipticum. We aimed to report the isolation and in vitro enzyme assays of stigmasterol using selected enzymes.