Computational analysis of zoanthamine alkaloids from Zoanthus sp. as potential DKK1 and GSK-3β inhibitors for osteoporosis therapy via Wnt signaling DOI Creative Commons

Ngoc-Thac Pham,

Huong-Giang Le,

Bo‐Rong Peng

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 24, 2025

Marine invertebrates are a rich source of structurally diverse secondary metabolites with broad biological activities, making them valuable for drug discovery. The genus Zoanthus is particularly noteworthy, producing numerous bioactive alkaloids, including the zoanthamines, which show promise in treating osteoporosis. Osteoporosis, debilitating bone disease characterized by reduced mineral density and increased fracture risk, linked to Wnt signaling pathway dysregulation. This highly conserved maintains tissue homeostasis crucial neurogenesis, synapse formation, development. Dickkopf-1 (DKK1) glycogen synthase kinase-3β (GSK-3β), key regulators, established therapeutic targets study employed an integrated computational approach-combining molecular docking, extensive dynamics (MD) simulations, functional theory (DFT) calculations-to assess inhibitory potential 69 zoanthamine-type alkaloids against DKK1 GSK-3β. MD analyzing root mean square deviation (RMSD), fluctuation (RMSF), radius gyration, free energy landscape, provided insights into protein-ligand complex stability interactions. Binding energies were calculated using MM-PBSA method combined interaction entropy. DFT calculations further elucidated electronic structure reactivity most promising inhibitors (3α-hydroxyzoanthenamine, epioxyzoanthamine, 7α-hydroxykuroshine E, norzoanthamine), exhibited favorable binding interactions residues target proteins. integrative approach demonstrates power methods discovery, highlighting zoanthamine as lead compounds innovative osteoporosis therapies.

Language: Английский

In Silico Approach for Antibacterial Discovery: PTML Modeling of Virtual Multi-Strain Inhibitors Against Staphylococcus aureus DOI Creative Commons
Valeria V. Kleandrova, M. Natália D. S. Cordeiro, M. Natália D. S. Cordeiro

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 196 - 196

Published: Jan. 31, 2025

Background/Objectives: Infectious diseases caused by Staphylococcus aureus (S. aureus) have become alarming health issues worldwide due to the ever-increasing emergence of multidrug resistance. In silico approaches can accelerate identification and/or design versatile antibacterial chemicals with ability target multiple S. strains varying degrees drug Here, we develop a perturbation theory machine learning model based on multilayer perceptron neural network (PTML-MLP) for prediction and virtual inhibitors against strains. Methods: To PTML-MLP model, chemical biological data associated activity were retrieved from ChEMBL database. We applied Box-Jenkins approach convert topological indices into multi-label graph-theoretical indices; latter used as inputs creation model. Results: The exhibited accuracy higher than 80% in both training test sets. physicochemical structural interpretation was performed through fragment-based (FBTD) approach. Such interpretations permitted analysis different molecular fragments favorable contributions multi-strain four new drug-like molecules using building blocks. designed predicted/confirmed our PTML diverse strains, thus representing promising chemotypes be considered future synthesis testing anti-S. agents. Conclusions: This work envisages applications modeling early discovery related antimicrobial research areas.

Language: Английский

Citations

3
Experimental and computational studies of Schiff bases derived from 4-aminoantipyrine as potential antibacterial and anticancer agents DOI Creative Commons
Johana Zúñiga-Miranda, Rebeca González‐Pastor, Saskya E. Carrera-Pacheco

et al.

Deleted Journal, Journal Year: 2025, Volume and Issue: 7(2)

Published: Jan. 31, 2025

Abstract Schiff bases are organic compounds recognized for their biological activities, including antiviral, antibacterial, antifungal, and anticancer properties, making them promising candidates in medicinal chemistry. In this studio, a series of 3a – h derived from 4-aminoantipyrine substituted cinnamaldehydes were evaluated vitro against liver (HepG2) thyroid (THJ29T) cancer cells, Gram-positive Gram-negative multidrug-resistant bacteria, biofilm-forming pathogens. Six demonstrated activity, though some exhibited toxicity to non-tumor cells. Compounds 3b , 3f 3h showed notable potential, while also strong antibacterial effects, with being the most effective bacteria strains. These inhibit biofilm formation, suggesting potential treating biofilm-related infections. In-silico analyses ADME global reactivity descriptors, binding affinities corroborated these findings. The base has affinity DNA gyrase vitamin D receptor, mechanisms its activities.

Language: Английский

Citations

0
Repurposing major metabolites of lamiaceae family as potential inhibitors of α-synuclein aggregation to alleviate neurodegenerative diseases: an in silico approach DOI Creative Commons
Soham Bhattacharya, Neha Gupta,

Adrish Dutta

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 16, 2025

Neurodegenerative disorders (NDs) are typically characterized by progressive loss of neuronal function and the deposition misfolded proteins in brain peripheral organs. They molecularly classified based on specific involved, underscoring critical role protein-processing systems their pathogenesis. Alpha-synuclein (α-syn) is a neural protein that crucial initiating progressing various NDs directly or indirectly regulating other ND-associated proteins. Therefore, reducing α-syn aggregation can be an excellent option for combating ND initiation progression. This study presents silico phytochemical-based approach discovering novel neuroprotective agents from bioactive compounds Lamiaceae family, highlighting potential computational methods such as functional networking, pathway enrichment analysis, molecular docking, simulation therapeutic discovery. Functional network analysis established direct indirect involvement NDs. Furthermore, docking interaction studies were conducted to screen 85 major family against aggregation. The results showed five (α-copaene, γ-eudesmol, carnosol, cedryl acetate, spathulenol) had high binding affinity towards with inhibitory activity its MD simulations validated stability interactions determined docking. In addition, pharmacokinetic underscores promising drug candidates, demonstrating blood-brain barrier (BBB) permeability, bioactivity, reduced toxicity. summary, this identifies most suitable targeting recommends these NDs, pending further vitro vivo validation.

Language: Английский

Citations

0
Computational analysis of zoanthamine alkaloids from Zoanthus sp. as potential DKK1 and GSK-3β inhibitors for osteoporosis therapy via Wnt signaling DOI Creative Commons

Ngoc-Thac Pham,

Huong-Giang Le,

Bo‐Rong Peng

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 24, 2025

Marine invertebrates are a rich source of structurally diverse secondary metabolites with broad biological activities, making them valuable for drug discovery. The genus Zoanthus is particularly noteworthy, producing numerous bioactive alkaloids, including the zoanthamines, which show promise in treating osteoporosis. Osteoporosis, debilitating bone disease characterized by reduced mineral density and increased fracture risk, linked to Wnt signaling pathway dysregulation. This highly conserved maintains tissue homeostasis crucial neurogenesis, synapse formation, development. Dickkopf-1 (DKK1) glycogen synthase kinase-3β (GSK-3β), key regulators, established therapeutic targets study employed an integrated computational approach-combining molecular docking, extensive dynamics (MD) simulations, functional theory (DFT) calculations-to assess inhibitory potential 69 zoanthamine-type alkaloids against DKK1 GSK-3β. MD analyzing root mean square deviation (RMSD), fluctuation (RMSF), radius gyration, free energy landscape, provided insights into protein-ligand complex stability interactions. Binding energies were calculated using MM-PBSA method combined interaction entropy. DFT calculations further elucidated electronic structure reactivity most promising inhibitors (3α-hydroxyzoanthenamine, epioxyzoanthamine, 7α-hydroxykuroshine E, norzoanthamine), exhibited favorable binding interactions residues target proteins. integrative approach demonstrates power methods discovery, highlighting zoanthamine as lead compounds innovative osteoporosis therapies.

Language: Английский

Citations

0