Synthesis and Molecular Docking Studies of Triazole Conjugated Novel 2,4-Disubstituted Thiazole Derivatives as CDK2 Inhibitors

Abstract

A series of triazole conjugated novel 2,4-disubstituted thiazole derivatives (9a-l) were synthesized from salicylaldehyde. These new chemical entities were characterized by their IR, ¹H & ¹³C NMR, mass spectral data and their molecular docking studies were performed to identify potential inhibitors of CDK2 protein. The synthesized analogs 9a-l were docked with CDK2 protein (PDB: 1GIJ). Among these 9h, 9j and 9k showed better Glide score, Prime MM-GBSA and ADME properties as compared to seliciclib and dinaciclib cancer inhibiting drugs of CDK2 protein. The amino acid Val83 of CDK2 protein was consistently binding to new chemical entities indicating that amino acid is crucial and responsible for its inhibition. Present findings suggested that compound 9h has 100% human oral absorption with highest Glide score -8.3 kcal/mol whereas drug molecules have feebler binding capacity and less Glide score indicating that the synthesized new chemical entity as potential inhibitor for CDK2 protein.