Design of novel hydrazide–hydrazone derivatives targeting MGC803 gastric cancer cell line by integrating 3D-QSAR, ADMET, network pharmacology, docking, MD simulations and biological efficacy

A Comprehensive Computational Investigation of Novel Hydrazide–Hydrazone Derivatives as Potential EGFR Inhibitors for Gastric Cancer Treatment

Findings support the Hydrazide–hydrazone derivatives' potential as EGFR kinase inhibitors, with M3 emerging as a particularly promising lead compound.

In Silico Optimization of Dihydropteridine Derivatives Targeting PLK1 for Glioblastoma: An Integrated QSAR, Docking, and Molecular Dynamics Study

Computational findings support the prioritization of X14 for further experimental validation in glioblastoma therapy, and generally favorable ADMET profiles were observed, hepatotoxicity alerts were predicted for all compounds, which represents an important limitation supporting the prioritization of X14.

Quinazolinone–hydroxamate derivatives as potential HDAC8 inhibitors: An integrated docking, ADME, DFT, and molecular dynamics study

Overall, this study identifies selected 4-oxoquinazoline hydroxamic acid derivatives as preliminary computational leads for further experimental validation as potential HDAC8-targeting compounds.

Design of novel derivatives of 1,3,4-thiadiazole against the α-amylase enzyme using 3D-QSAR, ADMET evaluation, docking analysis, molecular dynamic simulations and MM-PBSA approaches

Findings suggest that PR1 and PR2 are promising candidates for advanced antidiabetic drug development, exhibiting predicted enhanced inhibitory activities and favorable pharmacokinetic and toxicological profiles.

Molecular Modeling of Novel Hydrazide–Hydrazone Derivatives Bearing 5H-Chromen-5-one against HCT116 Human Colon Carcinoma Cells

Exploring Anti-Breast Cancer Potential and Mechanism of Novel Xanthohumol-Metformin Conjugate by Integrating Network Pharmacology, Molecular Docking and Simulation Approaches

Natural product scaffolds can be combined with repurposed drugs, so called conjugate molecules may exhibit improved pharmacology. We designed a conjugate (XN-MT) of xanthohumol (a prenylated chalcone with anticancer properties) and metformin (an antidiabetic drug with reported anticancer effects) and evaluated its potential against breast cancer (BC) using network-based pharmacology, docking, molecular dynamics (MD) simulation and density functional theory (DFT) Studies. Network pharmacology revealed targets relevant to cell proliferation, apoptosis, CDK4/2/1 signaling, and metabolic regulation and identified pathways were crucial for breast tumorigenesis and chemoresistance. Molecular docking against high-priority targets, like CDK4, PTGS2, and CDK1, predicted favourable binding affinities and plausible interaction modes for the conjugate. MD simulations (100 ns) for the conjugate showed stable ligandprotein interactions and persistent hydrogen bond networks, supporting the conjugates predicted binding stability. ADME, toxicity and DFT analyses provided comprehensive insights into the pharmacokinetic profile and electronic behaviour of xanthohumol, metformin and their conjugate. Moreover, DFT calculations on conjugates showed a lower HOMO-LUMO energy gap, average local ionization, decreased electrostatic potential, lower electron affinity, and higher chemical potential than xanthohumol, metformin, and Palbociclib, indicating greater reactivity and stronger receptor interactions. This integrative in-silico pipeline supports the XN-MT conjugate as a potential candidate for further in-vitro studies and preclinical development in breast cancer therapy targeting CDK4.