Blood pressure lowering effect of selected pyrimidine derivatives mediated through inhibition of calcium channel: A computational approach.

Irshad, Nadeem; Khan, Arif-ullah; Kamal, Yousaf; Iqbal, Muhammad Nasir

Pyrimidine 2, 4, 6-trione derivatives are known to have L-type calcium channel blockade activity due to which they are quite effective in cardiovascular diseases along with cancer, epilepsy and inflammatory disorders. The chemoinformatics prediction for test compounds: 5-(3-Hydroxybenzylidene)-2, 4, 6(1H, 3H, 5H)-pyrimidinetrione (SR-5), 5-(4-Hydroxybenzylidene)-2, 4, 6(1H, 3H, 5H)-pyrimidinetrione (SR-8), 5-(3-Chlorobenzylidene)-2, 4, 6(1H, 3H, 5H)-pyrimidinetrione (SR-9) and 5-(4-Chlorobenzylidene)-2, 4, 6(1H, 3H, 5H)-pyrimidinetrione (SR-10) was investigated. The druglikeliness and pharmacokinetic properties (PKs) of test compounds calculated using Molinspiration & Swiss ADME online servers. These test drugs subjected to molecular docking analysis and molecular dynamic (MD) simulation to calculate their binding energies with hypertensive and platelet aggregatory proteinaceous targets and their stability against calcium channel. The druggability and PKs of selected compounds exhibited that these compounds could be represented as potential candidates for further development into antihypertensive-like agents. The docking results indicated that binding energies ranged between -5 and -8.8 kcal/mol. Compounds showed good binding energies against calcium channels (CC) and subjected to molecular dynamic simulation to assess the stability of proteinligand complex. The results showed that all the ligands form stable complexes with the CC, though SR-9 and SR-10 had enhanced stability when compared to SR-5 and SR-8.

CALCIUM channels; BLOOD pressure; PYRIMIDINE derivatives; BINDING energy; MOLECULAR docking; PYRIMIDINES; ANTIHYPERTENSIVE agents

Pakistan Journal of Pharmaceutical Sciences, 2022, Vol 35, Issue 6, p1513

1011-601X

Academic Journal

10.36721/PJPS.2022.35.6.REG.1513-1522.1