Antimicrobial activity of synthetic bornyl benzoates against Trypanosoma cruzi

Abstract

We report here for the first time the in vitro effects of (1S,2R,4S)-1,7,7-trimethyl-bicyclo[2·2·1]heptan-2-yl-3',4',5'-trimethoxy benzoate (1) and (1S,2R,4S)-1,7,7-trimethyl-bicyclo[2·2·1]heptan-2-yl benzoate (2) on the growth and ultrastructure of Trypanosoma cruzi. These two synthetic compounds exerted an antiproliferative effect on the epimastigote forms of the parasite. The ICs(50/72h) of two synthetic L-bornyl benzoates, 1 and 2, was 10·1 and 12·8 μg/ml, respectively. Both compounds were more selective against epimastigotes than HEp-2 cells. Ultrastructural analysis revealed intense cytoplasmic vacuolization and the appearance of cytoplasmic materials surrounded by membranes. The treatment of peritoneal macrophages with compounds 1 and 2 caused a significant decrease in the number of T. cruzi-infected cells. L-Bornyl benzoate derivatives may serve as a potential source for the development of more effective and safer chemotherapeutic agents against T. cruzi infections.

Figure 1

Chemical structure of (1S,2R,4S)-1,7,7-trimethyl-bicyclo[2.2.1]heptan-2-yl-3′,4′,5′-trimethoxy benzoate (1) and (1S,2R,4S)-1,7,7-trimethyl-bicyclo[2.2.1]heptan-2-yl benzoate (2).

Figure 2

Effect of L-bornyl benzoates compounds 1 (gray bar) and 2 (black bar) on growth of epimastigotes of Trypanosoma cruzi Dm28c (A) and cytotoxicity to mammalian cells (B). The cells were cultured for 72 hours in the presence of indicated concentrations. The results are the average of two experiments in duplicate and expressed as percentage of growth inhibition or cytotoxicity in relation to untreated cells.

Figure 3

Effect of compounds 1 (b–c) and 2</emph> (d–e) on epimastigote forms of Trypanosoma cruzi after 72-hour treatment, as observed by transmission electron microscopy. (a) Untreated cell showing the normal morphology. (b–c) Treated cell with 10.1 μg/ml of compound 1. Note vacuoles containing cytoplasmic material (asterisk), and membrane aggregation (arrow). (d–e) Treated cell with 12.8 μg/ml of compound 2. Note the myelin-like figure inside of citoplasm (arrowhead) and vacuoles containing cytoplasmic material (asterisk). Scale bar = 1 μm. N, nucleus; K, kinetoplast.