Background: The chalcones were reported to have many biological activities by showing
affinity towards many enzymatic targets. The effect of nitric oxide (NO) on calcium channel was
extensively studied in different animals; the study was also carried out for NO donor drug and its
effect on calcium channel. Till date, the inhibition of calcium channel is of prime importance in the
medicinal chemistry to discover newer vascular smooth muscle relaxant drugs.
Objective: The main objective of this work is to carry out in silico and in vitro evaluation of NO
donor chalcones for calcium channel blocking potency.
Methods: The present work includes in silico evaluation of chalcone derivatives for calcium channel
blocking potency. The promising scaffolds were identified after pharmacophore modeling and docking
study. The in vitro screening of 21 lead molecules for calcium channel blocking potency was carried out
on pulmonary veins of adult goat, IC50 values were determined and 3D QSAR was performed.
Results: The pharmacophore modeling revealed that hydrogen bond donor, hydrogen bond acceptor,
and hydrophobic groups are important features for calcium channel blocking activity. The
docking study revealed the existence of hydrophobic, hydrogen bond and Vander wall's interactions
between amino acid residues and ligands. The in vitro screening showed that the compounds AI6,
Ca2, and D8 were potent, produced 4.756, 3.608 and 5.211 μM of IC50 respectively, whereas the
standard Nifedipine showed the potency of 1.304 μM of IC50. The 3D QSAR study explained the
importance of different steric and electrostatic parameters and their correlation for L type calcium
channel blocking activity.
Conclusion: This study showed that the chalcone scaffold with NO donor capacity is promising for
designing novel calcium channel blockers to treat vascular disorders.