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Current Computer-Aided Drug Design


ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

Research Article

Identification and Investigation of Chalcone Derivatives as Calcium Channel Blockers: Pharmacophore Modeling, Docking Studies, In vitro Screening, and 3D-QSAR Analysis

Author(s): Amol S. Sherikar*, Manish S. Bhatia and Rakesh P. Dhavale

Volume 17 , Issue 5 , 2021

Published on: 14 July, 2020

Page: [676 - 686] Pages: 11

DOI: 10.2174/1573409916666200714143930

Price: $65


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.

Keywords: In silico, 3D QSAR, pharmacophore modeling, docking, scaffold, vander walls.

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