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

Abstract

Calcium/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.