Novel Coumarin‐Pyrazole‐Thiazoles Hybrids: Synthesis, Anticancer Activity, Molecular Docking and In Silico ADMET prediction Studies

Abstract A novel series of coumarin‐pyrazole‐thiazoles hybrids was designed. The methodology depended on a simple condensation reaction of 3‐(2‐oxo‐2 H ‐chromen‐3‐yl)‐1‐phenyl‐1 H ‐pyrazole‐4‐carboxaldehyde with a variety of thiazole compounds having amino or active methylene groups. In addition, another series of 1‐(thiazol‐2‐yl)‐3‐(2‐oxo‐2 H ‐chromen‐3‐yl)‐1 H ‐pyrazole‐4‐carboxaldehydes was also achieved by applying Vilsmeier‐Haack formylation on 3‐1‐(2‐(thiazol‐2‐yl)hydrazineylideneethyl)‐2 H ‐chromen‐2‐ones. The obtained products were verified by spectral techniques such as IR, NMR, and mass spectra. To screen their abilities to inhibit cancer cell growth, these compounds were investigated against three tumor cell lines (MCF‐7, HepG2, and HCT116) using a standard method called SRB. The products 3 e , 7 b , 12 c and 14 a have considerable cytotoxic effects comparable to Doxorubicin. These products caused significant cell death by late apoptosis in all tumor cell lines. Furthermore, they preferentially induced G2 cell cycle arrest in MCF‐7 and HepG2 cells, while causing G1 cell cycle arrest in HCT116 cells. The molecular docking of these bioactive products showed good binding affinities with Cyclin‐dependent kinase 8 (CDK‐8). The ADMET‐predicted drug‐likeness properties of these bioactive compounds enable them to can used as promising anticancer agents.