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. Still date the inhibition of calcium
channel is prime importance in 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.
Method:
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.
Result:
The pharmacophore modeling revealed 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.
3D-QSAR Studies of Isatin Derivatives with Anti-Cancer In Vitro: Advanced CoMFA, CoMSIA and Docking Methods