Design, synthesis, and in silico studies of pyrazolyl-thiazole and thiazolidinone hybrids as potential antiproliferative agents

Breast and liver cancers are the most common causes of cancer death and finding new anticancer agents is critical. Inspired by their antitumor potential, thiazole and thiazolidinone derivatives bearing a pyrazole core were prepared from thiosemicarbazone unit through reactions with carbon electrophiles. Compared to doxorubicin and roscovitine, in vitro, antiproliferative activity against MCF7 and HepG2 cancer cell panels implied the most potency of 2,4-dihydroxybenzylidene- and 4-dimethylaminobenzylidene-thiazolidinone, being capable of powerful interactions with protein receptors. In density functional theory simulation, the dimethylaminobenzylidine-thiazolidine exhibited the lowest energy gap and highest softness values. Consistently, the superlative docking score toward CDK2 protein (PDB ID: 2A4L) was shown by later compound through hydrogen bonding, arene-hydrogen, and arene-cation interactions with key nucleobases and amino acids of CDK2 protein which might be potential CDK2 inhibitor. According to ADME study, these compounds showed good lipophilicity and oral bioavailability. This work may contribute to the advancing of new potent antiproliferative agents.