Antiamoeboid activity of squamins C–F, cyclooctapeptides from Annona globifora

Abstract

Free-living amoebae of Acanthamoeba spp. are causative agents of human infections such as granulomatous amoebic encephalitis (GAE) and Acanthamoeba keratitis (AK). The exploration of innovative chemical entities from natural sources that induce intrinsic apoptotic pathway or a Programmed Cell Death (PCD) in Acanthamoeba protozoa is essential to develop new therapeutic strategies. In this work, the antiamoeboid activity of squamins C–F ( 1 – 4 ), four cyclooctapeptides isolated from Annona globiflora was tested in vitro against Acanthamoeba castellanii Neff, A. polyphaga , A. quina , and A. griffini , and a structure–activity relationship was also established. The most sensitive strain against all tested cyclooctapeptides was A. castellanii Neff being the R conformers of the S-oxo-methionine residue, squamins D ( 2 ) and F ( 4 ), the most active against the trophozoite stage. It is remarkable that all four peptides showed no cytotoxic effects against murine macrophages cell line J774A.1. The analysis of the mode of action of squamins C–F against A. castellanii indicate that these cyclopeptides induced the mechanisms of programmed cell death (PCD). All peptides trigger mitochondrial damages, significant inhibition of ATP production compared to the negative control, chromatin condensation and slight damages in membrane that affects its permeability despite it conserves integrity at the IC 90 for 24 h. An increase in reactive oxygen species (ROS) was observed in all cases.

Gongolarones as antiamoeboid chemical scaffold

“…The cysticidal activity was evaluated by the alamarBlue® assay at 168 h and confirmed visually by inverted microscopy. Cysts of the Acanthamoeba strains were obtained as it has been described before [42,43]. First, 50 μL of 5⋅10 4 cysts/mL, as final concentration of mature cysts of Acanthamoeba strains, were cultivated in PYG medium in triplicate on a 96-well plate with 50 μL of serial dilutions of meroterpenes gongolarones A (1), C (3), and cystomexicone B (4).…”

Acción ixodicida de productos naturales de plantas nativas mexicanas

“…In general terms, the combined results of the adulticidal and larvicidal activity indicated that the methanolic extracts of Annona globiflora, Annona scleroderma, Litchi chinensis and Azadirachta indica have the best effectiveness. Annona genus has become a prolific producer of interesting compounds with great biological activity (36,37) . The acaricidal activities of the extracts of A. globiflora and A. scleroderma are possibly related to the presence of acetogenins, the main chemical constituents of the Annonaceae family, which have been found to have potent pesticidal activity against a variety of arthropods (38) .…”

Traditional Uses, Phytochemistry and Pharmacological Activities of Annonacae

“…Squamins C–F were isolated from the seeds of A. globifora and tested in vitro against trophozoites of Acanthamoeba spp. strains such as A. castellanii Neff, A. polyphaga , A. griffin and A. quina ( Table 8 ) [ 200 ]. All tested compounds exhibited antiamoeboid activity against the strains by inducing programmed cell death [ 200 ].…”

“…strains such as A. castellanii Neff, A. polyphaga , A. griffin and A. quina ( Table 8 ) [ 200 ]. All tested compounds exhibited antiamoeboid activity against the strains by inducing programmed cell death [ 200 ]. The same compounds were also tested for their cytotoxicity against murine macrophage cell line J774A.1 (ATCCTIB-67) and showed no cytotoxicity effect with CC 50 values greater than 200 μM [ 200 ].…”