Synthesis and Biological Evaluation of Novel Antihypertensive Compounds
Fernanda A. Ronchi1, §, Adriana B. Fernandes1, §, Rosana I. Reis1, Lys A. F. Mendes1, Luís G. Robello2, Paula C. Huber2, Patricia T. Baraldi2, Ricardo V. Marques3, Cláudio M. Costa-Neto4, Dulce E. Casarini1, *
Identifiers and Pagination:Year: 2016
First Page: 56
Last Page: 68
Publisher Id: CHEM-3-56
Article History:Received Date: 18/09/2014
Revision Received Date: 06/04/2015
Acceptance Date: 07/09/2015
Electronic publication date: 30/06/2016
Collection year: 2016
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
Hypertension has been associated as a pathogenesis involved in the renin angiotensin system. The most commonly used drug to block the AT1R, is Losartan which has specific pharmacophore groups such as imidazole and biphenyl. However the development of new selective antagonists would be advantagous to improving the treatment of hypertension. We investigated innovative antihypertensive candidates 1-3 using in vitro and in vivo assays.
Although only Compound 2 showed low affinity to the AT1R, it had no effect on blood pressure. Compound 1 produced a reduction in blood pressure and this effect seems to be mediated through ACE inhibition and not the blockage of the AT1R. Compound 1 was able to inhibit the ACE activity in a similar way to captopril, while Compounds 2 and 3 showed no effect on the enzyme activity.
Further studies need to be conducted to understand the mechanisms involved as well as signaling pathways.