MOLECULAR DOCKING STUDY OF SIDDHA FORMULATION SEENTHIL CHOORANAM TARGETING TRANSFORMING GROWTH FACTOR-Β1 (TGF-Β1) AND HUMAN PAPILLOMAVIRUS ONCOPROTEINS OF CERVICAL CARCINOMA

Abstract

Background: Cervical carcinoma remains one of the leading causes of cancer-related mortality among women worldwide, with persistent infection by high-risk Human Papillomavirus (HPV), particularly HPV-16, being the primary etiological factor. The HPV E6 oncoprotein and Transforming Growth Factor-β1 (TGF-β1) are key molecular targets involved in Cervical carcinogenesis, tumor progression, and metastasis. Seenthil Chooranam, a classical Siddha polyherbal formulation containing Tinospora cordifolia and Eclipta alba, is rich in bioactive phytoconstituents with reported anticancer properties. Objective: To investigate the molecular interactions and therapeutic potential of phytoconstituents of Seenthil Chooranam against HPV E6 oncoproteins and TGF-β1 using an integrated in silico approach. Methods: Twelve phytoconstituents were screened for drug-likeness using SwissADME, and seven compounds satisfying Lipinski's Rule of Five were further evaluated for ADMET properties using pkCSM. Molecular docking was performed using AutoDock Vina implemented in PyRx against HPV E6 proteins (PDB IDs: 4XR8 and 4GIX) and TGF-β1 (PDB ID: 1VJY). Protein–ligand interactions were analyzed using BIOVIA Discovery Studio Visualizer. Results: Seven phytoconstituents demonstrated favorable physicochemical properties and acceptable predicted pharmacokinetic profiles. Molecular docking revealed that Tinocordiside exhibited the highest binding affinity against HPV E6 proteins, with docking scores of −9.6 kcal/mol for 4XR8 and −8.5 kcal/mol for 4GIX, while Luteolin (−10.4 kcal/mol) and Apigenin (−10.3 kcal/mol) displayed binding affinities comparable to the standard ligand (−10.5 kcal/mol) against TGF-β1. Protein–ligand interaction analysis showed that the lead compounds established multiple conventional hydrogen bonds, carbon–hydrogen bonds, π-mediated interactions, hydrophobic contacts, and van der Waals interactions with key active-site residues, supporting stable protein–ligand complex formation. Conclusion: The findings suggest that the phytoconstituents of Seenthil Chooranam possess promising multitarget inhibitory potential against HPV E6 oncoproteins and TGF-β1, indicating their potential to simultaneously modulate viral oncogenic activity and host signaling pathways involved in Cervical cancer progression. Among the evaluated compounds, Tinocordiside emerged as the most promising inhibitor of HPV E6, whereas Luteolin and Apigenin demonstrated excellent binding affinity toward TGF-β1. Further experimental validation is warranted to confirm their therapeutic efficacy and safety.