Exploring Structure-based Drug Design for the Development of Multitarget Antihypertensives

Title:Exploring Structure-based Drug Design for the Development of Multitarget Antihypertensives

Volume: 12 Issue: 9

Author(s): Estella G. da Mota, Elaine F. F. da Cunha and Matheus P. Freitas

Affiliation:

Keywords: Antihypertensives, angiotensin converting-enzyme, calcium channel, rennin, docking studies, intermolecular interactions.

Abstract: This work reports the docking studies of compounds designed from the combination of substructures of three types of antihypertensives: angiotensin converting- enzyme (ACE) inhibitors, calcium channel blockers and renin inhibitors. Consequently, multi-target compounds are expected to be obtained. Indeed, a few purposes showed both docking scores and intermolecular ligand-enzyme interaction towards all three targets higher than the reference compounds Captopril (ACE inhibitor), Amlodipine (calcium channel blocker) and Aliskiren (renin inhibitor). Particularly, the proposed compound 18 (containing a phenyl group, a substituted dihydropyridine and a piperazinyl-like group as substituents at the indoline scaffold) is a promising ligand for all three enzymatic targets. These results, which were discussed in terms of ligand-enzyme interactions (especially hydrogen bonding between amino acid residues and ligands), indicate promising perspectives for synthesis and biological tests.

Cite this article as:

da Mota G. Estella, da Cunha F. F. Elaine and P. Freitas Matheus, Exploring Structure-based Drug Design for the Development of Multitarget Antihypertensives, Letters in Drug Design & Discovery 2015; 12 (9) . https://dx.doi.org/10.2174/1570180812666150331203528