Exploring the efficacy of some biologically active compounds as anti-hypertensive drugs: an insightful evaluation through DFT, molecular docking and molecular dynamics simulations.

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. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00291-4.