Pantnagar Journal of Research

Abstract

Ageing is characterized by progressive deterioration of cellular function driven by extracellular matrix degradation, chronic inflammation and dysregulated apoptosis, highlighting the need for safe bioactive compounds that target multiple ageing related pathways. The present study investigated the potential interactions of squalene with key molecular targets associated with ageing using an in silico molecular docking approach. Molecular docking was performed in PyRx using the AutoDock Vina scoring function against matrix etalloproteinase1 (MMP1), matrix metalloproteinase9 (MMP9), cyclooxygenase2 (COX 2), Tumour Necrosis Factor-α (TNF-α), hyaluronidase1 (HYAL1) and B cell lymphoma2 (Bcl2). Docking results were compared with established reference inhibitors, including marimastat, diclofenac, SPD304, garcinol and disarib. Squalene exhibited predicted binding affinities ranging from 7.4 to 8.6 kcal mol^¹, with the most favourable binding affinity observed for MMP9 (8.6 kcal mol^¹), followed by COX2 and Bcl2 (8.3 kcal mol^¹ each). Interaction analysis indicated that squalene predominantly formed hydrophobic alkyl, π-alkyl, π-sigma and van der Waals interactions within the binding pockets of the target proteins. These interaction profiles suggest that squalene may interact with multiple proteins involved in extracellular matrix remodelling, inflammatory signalling and apoptotic regulation. Overall, the findings provide preliminary computational evidence supporting the multi target interaction potential of squalene with ageing related proteins. However, these predictions require validation through molecular dynamics simulations and experimental in vitro and in vivo studies.