Pharmacological Activities of Novel Chromene Derivatives as Calcium/Calmodulin Dependent Protein Kinase IV (CAMKIV) Inhibitors

Abstract

AbstractCalcium/calmodulin dependent protein kinase IV (CAMKIV) phosphorylates various transcription activators and subsequently regulates cellular activities which triggered by CaMKK‐CAMKIV signalling. However, abnormal expression of CAMKIV is often associated with cancer and neurodegenerative diseases. We have synthesized and characterized a series of 3‐nitro‐2‐phenyl‐2H‐chromenes and tested their inhibition potential and binding affinity with the CAMKIV. Among the synthesised compounds, the IC50 value (50% of ATPase activity) for compounds D19 and D22 was observed as 12.22 ± 1.12 μM and 16.10 ± 1.30 μM respectively. The fluorescence binding and dot‐blot assay further complements inhibitory potential, indicating a better binding affinity. These compounds were tested against human cancerous cells (HepG2) and we observed a significant inhibition of cell viability, induced apoptosis and lowered tau‐phosphorylation. In cell viability studies, the IC50 values for compounds D19 and D22 was 18.33 ± 1.12 and 26.22 ± 1.30 μM respectively. These results suggested that the compounds D19 and D22 are non‐toxic to the normal cells and specifically inhibits the proliferation of cancerous cells.