Novel Thiazolidinedione Linked 1,3,4-Oxadiazole Derivatives as AXL Inhibitors Targeting Breast Cancer: In-Silico Design, ADMET Screening, and MM-GBSA Binding Free Energy

Abstract

A new series of thiazolidinedione linked 1,3,4oxadiazole hybrid analogs (T1-25) were designed by In-silico approach for their AXL inhibitor activity against breast cancer. Molecular docking studies were performed with binding pocket of AXLinhibitor (PDB ID: 5TD2) by using Schrodinger suit 2020-to elucidate the binding interactions of the newly designed targets. The docking studies were performed for all the designed molecules by Prime-MMGBSA module to determine free energy, In-silico ADMET screening by QikProp and Glide module. Based on the Glide score, the binding affinity of all the designed molecules towards AXL was chosen. AXL was inhibited by the designed molecules that have good hydrogen bonding interactions. The molecules (T1-25) have significant Glide scores in the range of -3.847 to -9.181 when compared with the standard Cyclophosphamide (-3.847) and 5-fluorouracil (-6.233). The In-silico molecular docking, ADMET properties were found within the suggested values. The MM-GBSA binding free energy results displayed very promising activity with the selected AXL inhibitor. The compounds T15, T19, T21 and T22 with highest Glide scores were found to be significant for anti-breast cancer activity.