Majumdar Sourav, Pramanik Anup
Department of Chemistry, Sidho-Kanho-Birsha University, Purulia, 723104 India.
In Silico Pharmacol. 2024 Dec 24;13(1):4. doi: 10.1007/s40203-024-00291-4. eCollection 2025.
Among different anti-hypertensive drugs, calcium channel blockers and human angiotensin-converting enzyme (ACE) inhibitors are the two main types. Herein, we took 25 biologically active ligands with potent anti-hypertensive activities and performed molecular docking studies with the human ACE receptor (PDB ID 1O8A) and human leukocyte antigens (HLA) complex, human voltage-dependent calcium channel alpha1 subunit (PDB ID 3LV3). Beforehand, we had performed density functional theory (DFT) studies to find out their structure-property relationships. In-silico ADMET studies were conducted, and we found that all 25 ligands follow Lipinski's Rule of 5, which confirms their oral bioavailability and high gastrointestinal absorption as a drug. Finally, molecular dynamics (MD) simulation studies were performed for the two top-scored drugs for 100 ns which reveal that a strong influence of the ligand (flunarizine) is there over the respective proteins.
The online version contains supplementary material available at 10.1007/s40203-024-00291-4.
在不同的抗高血压药物中，钙通道阻滞剂和人血管紧张素转换酶（ACE）抑制剂是两种主要类型。在此，我们选取了25种具有强效抗高血压活性的生物活性配体，并与人ACE受体（PDB ID 1O8A）、人白细胞抗原（HLA）复合物、人电压依赖性钙通道α1亚基（PDB ID 3LV3）进行了分子对接研究。在此之前，我们进行了密度泛函理论（DFT）研究以找出它们的结构-性质关系。进行了计算机辅助药物代谢动力学（ADMET）研究，我们发现所有25种配体均符合Lipinski的五规则，这证实了它们作为药物的口服生物利用度和高胃肠道吸收性。最后，对得分最高的两种药物进行了100纳秒的分子动力学（MD）模拟研究，结果表明配体（氟桂利嗪）对相应蛋白质有强烈影响。
在线版本包含可在10.1007/s40203-024-00291-4获取的补充材料。
