மருந்து வடிவமைத்தல்: திறந்த அணுகல்
திறந்த அணுகல்

சுருக்கம்

A Molecular Docking Approach to the Drug Inhibition of Endothelial Cell Adhesion Molecules Associated with Small Cell Lung Cancer Progression

Akshay P. Kulkarni

Small Cell Lung Cancer (SCLC) is a multistage, aggressive, metastatic form of lung cancer that accounts for about 13% of all lung cancer cases, with a 5-year survival rate of less than 6% mainly due to its metastatic component. The focus of metastatic SCLC has been focused on inhibiting the communication between SCLC circulating tumor cells and Cell Adhesion Molecules (CAMs) on endothelial cells, which cancer cells utilize to facilitate transmigration into a secondary tissue site after detaching from the primary tumor. It is well known that multiple CAMs are involved in SCLC transmigration; however, due to the different structures of CAM superfamilies involved in communication, efficient inhibitors to multiple CAMs have not been recognized. This study presents an in silico, molecular modeling approach to find potent inhibitors to multiple cell adhesion molecules involved in SCLC metastasis, including ICAM-1, VCAM-1, E-selectin, and P-selectin. From the ZINC15 database, 13 ligands of similar structure to Manassantin A and Casearinol A, two potent inhibitors of E-selectin and ICAM-1, were obtained and screened according to Lipinski’s Rule of 5. After preprocessing the proteins and ligands for docking, the ligands were blind docked to each CAM through AutoDock 4.0, and the binding affinities for each interaction were recorded. Docking results revealed four ligands (Ligands 8, 9, 10, 12) that recorded binding affinities significantly higher than that of Manassantin A and Casearinol A for E-selectin, P-selectin, and VCAM-1, while Ligand 11 (ZINC000146747094) recorded greater binding affinities than both controls across all four cell adhesion molecule groups. This study identified potent inhibitors against multiple cell adhesion molecules involved in SCLC tumor progression. Future experiments should test these inhibitors in vitro on SCLC cell lines to verify binding affinities.