New metabolically stable fatty acid amide ligands of cannabinoid receptors: synthesis and receptor affinity studies

We investigated the structure-activity relationships for the interactions of fatty acid amide analogs of the endocannabinoid anandamide with human recombinant cannabinoid receptors. Thirty-five novel fatty acid amides were synthesized using five different types of acyl chains and 11 different aromatic amine 'heads.' Although none of the new compounds was a more potent ligand than anandamide, we identified three amine groups capable of improving the metabolic stability of arachidonoylamides and their CBI/CB2 selectivity ratio to over 20-fold, and several aromatic amines capable of improving the affinity of short chain or monosaturated fatty acids for cannabinoid CBI receptors. For the first time a tertiary amide of arachidonic acid was found to possess moderate affinity (K, = 300 nM) for cannabinoid CBI, but not CB2, receptors

Biological and trophic consequences of genetic introgression between endemic and invasive Barbus fishes.

Genetic introgression with native species is recognized as a detrimental impact resulting from biological invasions involving taxonomically similar invaders. Whilst the underlying genetic mechanisms are increasingly understood, the ecological consequences of introgression are relatively less studied, despite their utility for increasing knowledge on how invasion impacts can manifest. Here, the ecological consequences of genetic introgression from an invasive congener were tested using the endemic barbel populations of central Italy, where the invader was the European barbel Barbus barbus. Four populations of native Barbus species (B. plebejus and B. tyberinus) were studied: two purebred and two completely introgressed with alien B. barbus. Across the four populations, differences in their biological traits (growth, body condition and population demographic structure) and trophic ecology (gut content analysis and stable isotope analysis) were tested. While all populations had similar body condition and were dominated by fish up to 2 years of age, the introgressed fish had substantially greater lengths at the same age, with maximum lengths 410-460 mm in hybrids versus 340-360 mm in native purebred barbel. The population characterized by the highest number of introgressed B. barbus alleles (81 %) had the largest trophic niche and a substantially lower trophic position than the other populations through its exploitation of a wider range of resources (e.g. small fishes and plants). These results attest that the genetic introgression of an invasive congener with native species can result in substantial ecological consequences, including the potential for cascading effects. Supplementary Information: The online version contains supplementary material available at 10.1007/s10530-021-02577-6

New metabolically stable fatty acid amide ligands of cannabinoid receptors: synthesis and receptor affinity studies

We investigated the structure-activity relationships for the interactions of fatty acid amide analogs of the endocannabinoid anandamide with human recombinant cannabinoid receptors. Thirty-five novel fatty acid amides were synthesized using five different types of acyl chains and 11 different aromatic amine 'heads.' Although none of the new compounds was a more potent ligand than anandamide, we identified three amine groups capable of improving the metabolic stability of arachidonoylamides and their CBI/CB2 selectivity ratio to over 20-fold, and several aromatic amines capable of improving the affinity of short chain or monosaturated fatty acids for cannabinoid CBI receptors. For the first time a tertiary amide of arachidonic acid was found to possess moderate affinity (K, = 300 nM) for cannabinoid CBI, but not CB2, receptors