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.

背景：据报道，查尔酮对许多酶靶点具有亲和力，因此具有许多生物活性。一氧化氮 (NO) 对钙通道的影响在不同的动物身上得到了广泛的研究；该研究还针对NO供体药物及其对钙通道的影响进行了研究。迄今为止，钙通道的抑制在药物化学中对于发现新的血管平滑肌松弛药物至关重要。

目的：这项工作的主要目的是对 NO 供体查耳酮的钙通道阻断效力进行计算机和体外评估。

方法：目前的工作包括对查尔酮衍生物的钙通道阻断效力进行计算机评估。在药效团建模和对接研究后确定了有前景的支架。对成年山羊的肺静脉进行了21种钙通道阻滞作用的铅分子的体外筛选，测定了IC ₅₀值并进行了3D QSAR。

结果：药效团模型显示，氢键供体、氢键受体和疏水基团是钙通道阻断活性的重要特征。对接研究揭示了氨基酸残基与配体之间存在疏水、氢键和范德壁相互作用。体外筛选显示化合物AI6、Ca2和D8是有效的，分别产生4.756、3.608和5.211 μM的IC ₅₀，而标准硝苯地平显示出1.304 μM的IC ₅₀的效力。3D QSAR 研究解释了不同空间和静电参数的重要性及其对 L 型钙通道阻断活性的相关性。

结论：本研究表明，具有 NO 供体能力的查耳酮支架有望用于设计治疗血管疾病的新型钙通道阻滞剂。