Anna Rodríguez

First fossil evidence of an “interglacial refugium” in the Pyrenean region

A refugium is generally understood as an area where temperate species survive cold periods, such as the Iberian, Italian, or Balkan Peninsulas in Europe. Strictly speaking, this definition refers to what is known as a glacial refugium. However, there are various types of lesser-known refugia such as the interglacial refugium, which denotes a mountainous region at low latitudes, such as the Pyrenees, where species adapted to the cold survive during interstadial periods. The small-vertebrate association from the sequence of Cova Colomera, which is located on the southern face of the Pyrenees and contains the final cold spell of the Late Pleistocene and the beginnings of the temperate period in which we currently find ourselves (the Holocene), could constitute the first fossil evidence of such an interglacial refugium, thus providing new paleoecological data on the phenomenon.

New selective A2A agonists and A3 antagonists for human adenosine receptors: synthesis, biological activity and molecular docking studies

We report the synthesis and pharmacological characterization of a new series of adenosine derivatives on the four adenosine receptors (ARs). In radioligand binding assays, some of the compounds (1, 4, 6 and (R)-6) display a potent affinity for the A2AAR (Ki values < 10 nM) with high A1/A2A and A2B/A2A selectivity, moderate for the A3AR and low for the A1AR. The affinity of the epimeric mixture 6 was similar to that of the corresponding (R)-6 stereoisomer and 10-fold higher than that of the (S)-6 stereoisomer. The phenylethylamino group appears to play a key role on the activity, but introduction of groups of different sizes and electronegativity does not induce a substantial change in affinity for the A2AAR. In functional assays, most of the compounds produced similar amounts of cAMP compared to NECA, thus behaving as full A2AAR agonists. In addition, compounds 1, 2, 3, 5, (S)-6 and 9 resulted to be good antagonists for A3AR with KB in the 6–14 nM range. Docking studies on the A2AAR showed a conserved binding mode consistent with previous A2AAR agonist-bound crystal structures, allowing for a rational interpretation of the SAR of this compound series.