In Silico Molecular Docking and SwissADME Prediction of Cinnamaldehyde Protection Against the PbO Ps ‐Induced Morphological and Histopathological Teratogenicity

Background This study investigated the antiteratogenic effects of cinnamaldehyde against lead oxide nanoparticulate (PbO‐Ps)‐induced developmental toxicity in chick embryos. Methods PbO‐Ps were synthesized using a chemical method and characterized by UV–Vis spectroscopy, FTIR, and SEM. Fertilized Gallus gallus domesticus eggs ( n = 56) were randomly assigned to four experimental groups: procedural control (sterile normal saline), PbO‐Ps (33 μg/egg), PbO‐Ps plus low‐dose cinnamaldehyde (33 + 33.2 μg/egg), and PbO‐Ps plus high‐dose cinnamaldehyde (33 + 66.4 μg/egg). Morphological and histopathological outcomes were assessed. ANOVA was performed to compare outcomes among groups. Molecular docking using AutoDock 4.2 evaluated interactions of cinnamaldehyde with apo p110α/p85α, apo p110δ/p85α, and PTEN. Drug‐likeness and pharmacokinetic properties were evaluated using SwissADME. Results PbO‐Ps characterization revealed a characteristic absorption peak at 236 nm, Pb–O vibrations at 450–550 cm − ¹, and irregular plate‐like particles with apparent sizes of approximately 100–400 nm. On Day 14, PbO‐Ps exposure caused growth retardation, limb and craniofacial deformities, and poor feather development. Persistent morphological abnormalities, impaired movement, and poor coordination were observed after Day 21 in the PbO‐Ps group compared with controls. Cinnamaldehyde ameliorated these effects, with significantly greater protection observed at the higher dose ( p < 0.05). Severe hepatic, neuronal, and cardiac tissue damage was observed following PbO‐Ps exposure, whereas cinnamaldehyde reduced histopathological abnormalities in a dose‐dependent manner. Molecular docking showed that cinnamaldehyde interacted with all three target proteins, with the strongest binding affinity observed for apo p110α/p85α. Conclusions The findings indicate that high‐dose cinnamaldehyde significantly mitigated PbO‐Ps‐induced developmental toxicity and teratogenicity in chick embryos. Further studies, including molecular dynamics simulations and long‐term in vivo investigations, are warranted to clarify the underlying protective mechanisms and evaluate post‐hatch effects.