Instituto de Productos Naturales y Agrobiología

A simple epimerization of C-(α-D-Gly p )methanol into C-(β-L-Gly p )methanol compounds is described. The radical sequence involved homolytic cleavage of the C5–H bond by 1,5-hydrogen atom transfer promoted by the 1’-O-yl radical and subsequent hydride addition with inversion of configuration. This methodology allows the preparation of rare C-(β-L-Ido p )-, C-(β-L-Altp)-, C-(β-L-Gulp)-, C-(β-L-Allp)methanol glycosides starting from carbohydrates of the D-series. It can also be applied to transform L- into D-configured C-glycosyl compounds, as illustrated by the formation of C-(β-D-6dGulp)- and C-(β-D-6dAltp)methanol from readily accessible L-rhamno and L-fuco analogs, respectively. In further development of this procedure compounds with C-(β-L-Araf)- and C-(β-L-5dRibf)methanol structures have also been synthesized. The alkoxyl radicals were generated by reaction of the corresponding N-alkoxyphthalimides with nBu3SnH(D) and in comparative terms, by visible light-photocatalysis using the Hantzsch ester/fac-Ir(ppy)3 procedure. The influence of the sugar ring conformation and the electronegativity of the substituents on the stereochemical outcome will be addressed.

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 IC90 for 24 h. An increase in reactive oxygen species (ROS) was observed in all cases.

Invasive snakes represent a serious threat to island biodiversity, being responsible for far-reaching impacts that are noticeably understudied, particularly regarding native reptiles. We analysed the impact of the invasive California kingsnake, Lampropeltis californiae—recently introduced in the Canary Islands—on the abundance of all endemic herpetofauna of the island of Gran Canaria. We quantified the density in invaded and uninvaded sites for the Gran Canaria giant lizard, Gallotia stehlini, the Gran Canaria skink, Chalcides sexlineatus, and Boettger's wall gecko, Tarentola boettgeri. We used spatially explicit capture-recapture and distance-sampling methods for G. stehlini and active searches under rocks for the abundance of the other two reptiles. The abundance of all species was lower in invaded sites, with a reduction in the number of individuals greater than 90% for G. stehlini, greater than 80% for C. sexlineatus and greater than 50% for T. boettgeri in invaded sites. Our results illustrate the severe impact of L. californiae on the endemic herpetofauna of Gran Canaria and highlight the need for strengthened measures to manage this invasion. We also provide further evidence of the negative consequences of invasive snakes on island reptiles and emphasize the need for further research on this matter on islands worldwide.