Exploring Structure-based Drug Design for the Development of Multitarget Antihypertensives
Estella G. da Mota,
Elaine F. F. da Cunha,
Matheus P. Freitas.
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.
Keywords: Antihypertensives, angiotensin converting-enzyme, calcium channel, rennin, docking
studies, intermolecular interactions.
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