Comparative toxicity assessment of fisetin-aided artificial intelligence-assisted drug design targeting epibulbar dermoid through phytochemicals

Abstract

Abstract Epibulbar dermoid, benign tumors resulting from the improper function of the pathogenic protein Patched 1 (PTCH1), surgical interventions are employed to mitigate the lethal effects. However, these procedures often lead to complications such as scleral weakening and corneal astigmatism. Due to the absence of effective medical treatments, there is a critical need for novel approaches to prevent the spread of this disease. This study not only fills a key gap in medical therapy for epibulbar dermoid, but it also demonstrates AI’s transformational potential in drug development. Employing an AI drug design service, three efficient de novo therapeutic compounds targeting the PTCH1 protein were crafted with Fisetin. The method included obtaining the PTCH1 protein sequence from NCBI, computing physiochemical parameters with Expasy Protparam, and estimating the 3D structure with SWISS-MODEL. Quality assessment, binding site prediction, drug design with WADDAICA, Lipinski’s Rule of 5, toxicity screening, ADMET evaluation, docking analysis with CB-dock and Patch dock, and MD simulations with IMOD all work together to provide an adequate basis for the development and validation of AI-designed phytochemical medicines for epibulbar dermoid. Comprehensive pharmacokinetic and toxicity assessments demonstrated the outstanding absorbency of AI-designed Fisetin in the blood–brain barrier, emphasizing its non-toxic nature. The AI-designed Fisetin exhibits a notable affinity of approximately −9.2 kcal/mol during docking with the PTCH1 protein, suggesting its potential as a drug. While the in silico results indicate efficiency and safety, the necessity for in vivo testing is acknowledged to validate these promising findings. This research significantly advances the frontier of knowledge by proposing a non-invasive solution to epibulbar dermoid, addressing current limitations, and offering potential alternatives to conventional surgical interventions.