In-silico Evaluation of Allium sativum Derived Phytochemicals Reveals Promising Drug Candidates for p53-MDM2 Interaction in Osteosarcoma Therapy

Abstract

Osteosarcoma is a rare but aggressive bone cancer with poor prognosis, largely due to chemoresistance and the absence of effective targeted therapies. The MDM2 oncoprotein, a negative regulator of the p53 tumour suppressor, has emerged as a key driver of osteosarcoma progression and drug resistance. While synthetic MDM2 inhibitors have shown potential, concerns over toxicity, poor selectivity, and limited clinical success have prompted the search for safer, natural alternatives. This study employed an integrated computer-aided drug design approach to identify Allium sativum-derived phytochemicals as potential MDM2 inhibitors for osteosarcoma therapy. A total of 154 bioactive compounds identified through GC-MS analysis were screened against the crystal structure of MDM2 using molecular docking. Further filtering based on drug-likeness and ADMET predictions led to the identification of three lead compounds—gallic acid, cis-13,16-docosadienoic acid, and p-toluic acid heptadecyl ester—with favourable pharmacokinetic properties and potential binding stability. These compounds demonstrated better predicted affinity and safety profiles than the standard drug doxorubicin, suggesting possible therapeutic relevance. While these findings provide promising insight into the use of natural compounds targeting the p53-MDM2 axis, it is important to note that experimental validation through in-vitro and in-vivo studies is essential to confirm their efficacy and clinical potential in osteosarcoma therapy.