In vitro and in vivo studies of the biological activity of novel arylimidamides against Trypanosoma cruzi

J S De Araújo; C F Da Silva; D G J Batista; P B Da Silva; M B Meuser; C A F Aiub; M F V da Silva; C F Araújo-Lima; M Banerjee; A A Farahat; C E Stephens; A Kumar; D W Boykin; M N C Soeiro

doi:10.1128/AAC.01403-13

In vitro and in vivo studies of the biological activity of novel arylimidamides against Trypanosoma cruzi

Antimicrob Agents Chemother. 2014 Jul;58(7):4191-5. doi: 10.1128/AAC.01403-13. Epub 2014 Mar 3.

Authors

J S De Araújo¹, C F Da Silva¹, D G J Batista¹, P B Da Silva¹, M B Meuser¹, C A F Aiub², M F V da Silva², C F Araújo-Lima³, M Banerjee⁴, A A Farahat⁵, C E Stephens⁶, A Kumar⁴, D W Boykin⁴, M N C Soeiro⁷

Affiliations

¹ Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
² Departamento de Genética e Biologia Molecular, Universidade do Estado do Rio de Janeiro, Instituto Biomédico, Departamento de Genética e Biologia Molecular, Laboratório de Genotoxicidade, Rio de Janeiro, Brazil.
³ Departamento de Biofísica e Biometria, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
⁴ Department of Chemistry, Georgia State University, Atlanta, Georgia, USA.
⁵ Department of Chemistry, Georgia State University, Atlanta, Georgia, USA Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
⁶ Department of Chemistry and Physics, Georgia Regents University, Augusta, Georgia, USA.
⁷ Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil soeiro@ioc.fiocruz.br.

Abstract

Fifteen novel arylimidamides (AIAs) (6 bis-amidino and 9 mono-amidino analogues) were assayed against Trypanosoma cruzi in vitro and in vivo. All the bis-AIAs were more effective than the mono-AIAs, and two analogues, DB1967 and DB1989, were further evaluated in vivo. Although both of them reduced parasitemia, protection against mortality was not achieved. Our results show that the number of amidino-terminal units affects the efficacy of arylimidamides against T. cruzi.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amidines / chemistry
Amidines / therapeutic use*
Animals
Chagas Disease / drug therapy*
Chagas Disease / mortality
Chagas Disease / parasitology
Male
Mice
Parasitemia / drug therapy*
Parasitemia / mortality
Parasitemia / parasitology
Parasitic Sensitivity Tests
Trypanocidal Agents / chemistry
Trypanocidal Agents / therapeutic use*
Trypanosoma cruzi / drug effects*

Substances

Amidines
Trypanocidal Agents