Aug 2026· In Silico Pharmacology· Vol 14· 0 citations· 35 references
Medicine
TL;DR
A cost-effective computational workflow for prioritizing ENR inhibitors is demonstrated, providing a foundation for the development of novel antimalarial agents and highlighting Cd3 and Cd5 as the most promising candidates for further development.
This study highlights natural diterpenoids and coumarin glycosides as promising scaffolds for caspase-1 inhibition and demonstrates that integrating QSAR modeling with structure-based approaches provides an efficient strategy for discovering potential anti-inflammatory drug candidates.
Yusuf Şeflekçi, Alper Yılmaz, Abdulilah Ece· Molecules· 0 citations
The findings suggest that Lig-1, followed by Lig-3, may serve as promising computational lead compounds targeting SARS-CoV-2 MPro, representing promising candidates for further experimental validation.
Mohd Yasir Khan, Farah Maarfi, A. Shah et al.· International Journal of Mol...· 0 citations
Overall, this study identifies selected 4-oxoquinazoline hydroxamic acid derivatives as preliminary computational leads for further experimental validation as potential HDAC8-targeting compounds.
D. Saleem, M. Mahdi, Ayad Mohammed Rasheed· Pharmacia· 0 citations
Plasmodium falciparum Calcium-Dependent Protein Kinase 4 (PfCDPK4) is a validated target for malaria transmission-blocking interventions, as its inhibition disrupts male gametocyte exflagellation. Hexahydroquinolines (HHQs) have emerged as promising gametocytocidal agents. This study aimed to design novel HHQs as potential PfCDPK4 inhibitors with good binding affinity, favourable pharmacokinetics, and structural stability. A library of 20,000 novel HHQ analogs was generated using genetic algorithm-driven de novo molecular design in AlvaBuilder and systematically filtered through a pipeline comprising machine-learning-based bioactivity prediction, PAINS removal, pharmacophore modeling, ADMET screening, and structure-based virtual screening. Top-ranking compounds underwent bioisosteric optimization and were evaluated using 300 ns molecular dynamics simulations and density functional theory (DFT) calculations. Comparative in silico validation against known inhibitor Bumped Kinase Inhibitor-1 (BKI-1) and the co-crystallized ligand DXR as controls demonstrated that four HHQ analogs exhibited comparable binding affinities and stable interactions with key residues within the ATP-binding pocket. Favourable ADMET profiles, dynamic stability, and supportive electronic properties further reinforced their inhibition potential. These findings provide biologically meaningful computational evidence supporting HHQ scaffolds as potential PfCDPK4 inhibitors and demonstrate the utility of integrated bioinformatics approaches for malaria transmission-blocking drug discovery. Further experimental validation is required to confirm the inhibitory activities of the identified hexahydroquinoline compounds.
G. Oduselu, D. Bodun, O. Ajani et al.· Bioinformatics and Biology I...· 0 citations
The MGC803 cell line is a human gastric cancer model frequently used in cancer research. In this context, a combined in silico approach including 3D-QSAR modeling, ADMET analysis, network pharmacology, docking, molecular dynamics and ligand transport evaluations, was applied to design new antiproliferative molecules. A robust 3D-QSAR model with high predictive capacity (R² and Q²) was developed and used to design new compounds (PR1–PR4). After an ADMET screening, the putative biological targets of the non-toxic compounds were predicted using PharmMapper. A network pharmacology analysis identified several hub genes, of which HSP90AA1 had the highest degree value. Given its central role in stabilizing multiple oncogenic proteins involved in gastric cancer progression, as well as its suitability for structure-based studies, HSP90AA1 was selected for molecular docking and molecular dynamics simulations. In addition, molecular docking was performed on HSP90AA1 protein (1YET) in complex with the designed molecules (PR1-PR4), and their predicted binding behaviors were compared to both the most active molecule (M34) and the reference drug, geldanamycin. These results demonstrate a high predicted binding affinity and remarkable interaction profiles within the active site of the HSP90AA1. To further evaluate the dynamic stability of these complexes, we performed molecular dynamics simulations over a 100 ns period, thus confirming stable attachment modes and durable contact networks. The MM-PBSA approach demonstrated favorable binding free energies between the chosen PR4 ligand and the 1YET protein (-26.47 ± 2.89 kcal/mol). Finally, the ligand transport study showed that the PR4 ligand easily crosses tunnels 1 and 2 with optimal theoretical transport dynamics compared to the reference drug, geldanamycin (GA). This comprehensive computational method underlines the diverse potential of the examined molecules, identifying the most promising candidates for subsequent experimental validation against gastric cancer.
L. Naanaai, Abdellah El Aissouq, Yassine El Allouche et al.· Beni-Suef University Journal...· 0 citations
An integrated computational strategy involving pharmacophore mapping, molecular docking, molecular dynamics simulations, and density functional theory (DFT) analysis was employed to identify potential SaFtsZ inhibitors, highlighting compound 15 as a computationally predicted scaffold for the development of SaFtsZ-targeted antibacterial agents.
Sundarrajan T., Neerugatti Dora Babu, A. K. N. et al.· RSC Advances· 0 citations
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