In Silico Assessment of the Insecticidal and Herbicidal Potential of Silichristin Isolated from Silybum Marianum: Pharmacokinetic-Toxicity properties, Molecular Docking, and Molecular Dynamics

The present study aims to evaluate the pesticidal potential of a series of novel silichristin analogues isolated from silybum marianum using in silico approaches, focusing on their effects on the 4-hydroxyphenylpyruvate dioxygenase (HPPD) and acetylcholinesterase (AChE) receptors. A combinatorial library of 729 silichristin derivatives was constructed and virtual screening was performed to evaluate their pharmacokinetic and toxicity properties. Molecular docking analyses were performed to assess the binding affinity of the most potent candidates with target proteins. Our findings revealed that all selected compounds exhibited activity against both HPPD and AChE, with SIL3 and SIL7 demonstrating the lowest binding free energies (-8.4 and -7.9 kcal/mol, respectively). Further investigation via molecular dynamic simulation indicated that SIL3 and SIL7remained stable within the HPPD and AChE active sites, with RMSD values consistently below 2Å throughout the simulation. Overall, these results suggest that the newly identified silichristin derivatives hold promise as anti-pesticide agents.