Piperamides and their derivatives as potential anti-trypanosomal agents

Author(s)

Cotinguiba, Fernando ^[1] ; Regasini, Luis Octavio ^[1] ; Bolzani, Vanderlan da Silva ^[1] ; Debonsi, Hosana Maria ^[2] ; Passerini, Gabriela Duo ^[3] ; Barretto Cicarelli, Regina Maria ^[3] ; Kato, Massuo Jorge ^[4] ; Furlan, Maysa ^[1]

Affiliation

^[1] Univ Estadual Paulista UNESP, Inst Quim, BR-14801970 Araraquara, SP - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Univ Estadual Paulista UNESP, Fac Ciencias Farmaceut, BR-14801902 Araraquara, SP - Brazil

^[4] Univ Sao Paulo, Inst Quim, BR-05508900 Sao Paulo - Brazil

• Document type: Journal article
• Source: MEDICINAL CHEMISTRY RESEARCH; v. 18, n. 9, p. 703-711, DEC 2009.
• Web of Science Citations: 49

Abstract

We describe herein an evaluation of the trypanocidal effect of eight piperamides (1-8) isolated from Piper tuberculatum bearing dihydropyridone, piperidine, and isobutyl moieties against epimastigote forms of Trypanosoma cruzi, the causative agent of Chagas' disease. Based on such results, three hydrogenated and two hydrolyzed derivatives (10-14) were prepared and evaluated as well. The dihydropyridone amides (1-3) displayed higher anti-trypanosomal activity. The (Z)-piplartine (1) showed higher activity with a 50% inhibition concentration (IC(50)) value of 10.5 mu M, almost four times more potent than the positive control, benznidazole (IC(50) = 42.7 mu M), and should be further evaluated as a suitable hit for the design of new antiprotozoal agents. (AU)

• FAPESP's process: 03/00886-7 - Phytochemical study of Pterogyne nitens (Leguminosae), synthesis and pharmacological evaluation of natural guandine alkaloids and of potential antitumoral analogues
• Grantee: Luis Octávio Regasini
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)