M. Angeles Cabello

Screening of basidiomycetes for antimicrobial activities.

As a part of a screening programme developed to evaluate the antimicrobial activity of basidiomycetes, 317 isolates representing 204 species collected in Spain were screened against a range of human clinical pathogens and laboratory controls. Extracts from 45% of the isolates, representing 109 species, showed antimicrobial activity. Antibacterial activity was more pronounced than antifungal activity. The proportion of extracts from basidiomycetes showing antimicrobial activity was similar to or above that obtained for representative orders of Ascomycetes, such as Pezizales and Xylariales, but lower than that produced by members of the orders Diaporthales, Eurotiales, Hypocreales, Leotiales and Sordariales. Suprageneric taxa (orders and families) did not show pronounced differences in their antimicrobial activities though such differences were observed at the genus level, suggesting that the ability to produce these bioactive compounds is not homogenously distributed amongst the basidiomycetes. Isolates from some species showed large differences in their ability to produce metabolites with antimicrobial activity, possibly reflecting genetic differences at the infraspecific level.

Potent and Selective Peptide Agonists of α‐Melanocyte Stimulating Hormone (αMSH) Action at Human Melanocortin Receptor 5; their Synthesis and Biological Evaluation in vitro

Melanocortin receptors (MC1‐5R) and their endogenous ligands (melanocyte‐stimulating hormones and adrenocorticotropic hormone) are involved in many physiological processes in humans. Of those receptors, the actions of MC5R are the least understood despite its broad presence in the numerous peripheral tissues and brain. In this study, we describe synthesis and pharmacological properties in vitro (receptor‐binding affinity and agonist activity) of several cyclic analogs of αMSH which are potent agonists at hMC5R (EC50 below 1 nm) and of enhanced receptor subtype selectivity (more than 2000‐fold versus hMC1b,3R and about 70‐ to 200‐fold versus hMC4R). These compounds are analogs of Ac‐Nle4‐cyclo[Asp5–His6‐D‐Nal(2′)7–Pip8–Trp9–Lys10]–NH2 (Pip: pipecolic acid) in which His6 has been replaced with sterically hindered amino acids. They may be useful tools in the elucidation of the MC5R role in skin disorders and in immunomodulatory and in anti‐inflammatory actions of αMSH.