Open Chemistry Journal

2016, 3 : 56-68
Published online 2016 June 30. DOI: 10.2174/1874842201603010056
Publisher ID: CHEM-3-56

RESEARCH ARTICLE
 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 and Dulce E. Casarini1, *
1 Disciplina de Nefrologia, Departamento de Medicina, Universidade Federal de São Paulo, Rua Botucatu, 740, CEP: 04023-900, Vila Clementino, São Paulo, Brazil
2 Instituto Vita Nova, Laboratório de Síntese Orgânica. Rua Barão de Itapura, 135, CEP: 13186-432, Parque Odimar, Hortolândia, São Paulo, Brazil
3 EMS S.A., Rodovia Jornalista Francisco Aguirre Proença SP – SP 101 Km 8 Chácara Assay, Hortolândia, São Paulo, Brazil
4 Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. Avenida dos Bandeirantes, 3.900, CEP: 14049-900, Ribeirão Preto, Brazil

* Address correspondence to this author at the Department of Medicine, Nephrology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo – São Paulo, Botucatu Street, 740, zip code 04023-900, São Paulo, SP, Brazil; Tel: 55 11 5904 1685; Fax: 55 11 5904 1684; E-mails: , decasarini@gmail.com

ABSTRACT

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.

Keywords:

ACE, AT1 Receptor, Binding, Blood Pressure, CHO Cells, Hypertension, Imidazole, Pharmacophore Group, Renin Angiotensin System.