Gibbilimbol analogues as antiparasitic agents-Synthesis and biological activity against Trypanosoma cruzi and Leishmania (L.) infantum

Author(s)

Varela, Marina T. ^[1] ; Dias, Roberto Z. ^[1] ; Martins, Ligia F. ^[2] ; Ferreira, Daiane D. ^[2] ; Tempone, Andre G. ^[2] ; Ueno, Anderson K. ^[1] ; Lago, Joao Henrique G. ^[1] ; Fernandes, Joao Paulo S. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Rua Sao Nicolau 210, BR-09913030 Diadema, SP - Brazil

^[2] Adolfo Lutz Inst, Ctr Parasitol & Micol, Ave Dr Arnaldo 355, BR-01246902 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Bioorganic & Medicinal Chemistry Letters; v. 26, n. 4, p. 1180-1183, FEB 15 2016.
• Web of Science Citations: 8

Abstract

The essential oils from leaves of Piper malacophyllum (Piperaceae) showed to be mainly composed by two alkenylphenol derivatives: gibbilimbols A and B. After isolation and structural characterization by NMR and MS data analysis, both compounds were evaluated against promastigote/amastigote forms of Leishmania (L.) infantum as well as trypomastigote/amastigote forms of Trypanosoma cruzi. The obtained results indicated that gibbilimbol B displayed potential against the tested parasites and low toxicity to mammalian cells, stimulating the preparation of several quite simple synthetic analogues in order to improve its activity and to explore the preliminary structure-activity relationships (SAR) data. Among the prepared derivatives, compound LINS03003 (n-octyl-4-hydroxybenzylamine) displayed the most potent IC50 values of 5.5 and 1.8 mu M against amastigotes of T. cruzi and L. (L.) infantum, respectively, indicating higher activity than the natural prototype. In addition, this compound showed remarkable selectivity index (SI) towards the intracellular forms of Leishmania (SI = 13.1) and T. cruzi (SI = 4.3). Therefore, this work indicated that preparation of synthetic compounds structurally based in the bioactive natural products could be an interesting source of novel and selective compounds against these protozoan parasites. (C) 2016 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 13/20479-9 - Synthesis and evaluation of compounds potentially ligands of H4 receptors
• Grantee: João Paulo dos Santos Fernandes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/18756-1 - Evaluation of novel alternative therapies with synthetic drugs using in vitro and experimental models of Leishmania (L.) infantum chagasi
• Grantee: André Gustavo Tempone Cardoso
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/11936-2 - Use of chemodiversity of plant species in remaining areas of Atlantic Forest from São Paulo State in the selection of biologically active prototypes
• Grantee: João Henrique Ghilardi Lago
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/16564-3 - Synthesis and evaluation of activity of gibbilimbol B derivatives in Trypanosoma cruzi
• Grantee: Marina Themoteo Varela
• Support Opportunities: Scholarships in Brazil - Scientific Initiation