Here we designed and synthesized analogs of two antimicrobial peptides, namely C10:0-A2, a lipopeptide, and TA4, a cationic α-helical amphipathic peptide, and used non-proteinogenic amino acids to improve their therapeutic properties. The physicochemical properties of these analogs were analyzed, including their retention time, hydrophobicity, and critical micelle concentration, as well as their antimicrobial activity against gram-positive and gram-negative bacteria and yeast. Our results showed that substitution with D- and N-methyl amino acids could be a useful strategy to modulate the therapeutic properties of antimicrobial peptides and lipopeptides, including enhancing stability against enzymatic degradation. The study provides insights into the design and optimization of antimicrobial peptides to achieve improved stability and therapeutic efficacy. TA4(dK), C10:0-A2(6-NMeLys), and C10:0-A2(9-NMeLys) were identified as the most promising molecules for further studies.

Natural products represent a rich source of bioactive compounds that have been historically used to obtain substances with great medicinal potential. The skin of anuran amphibians is a rich source of compounds with a wide range of biological activity. Alzheimer's disease (AD) is a complex disease associated with all kind of different pathways, making their simultaneous modulation necessary. Nowadays anti-AD treatments are focused on enzymatic inhibitors. Here in we report the activity of skin extracts from nine species from Argentina, belonging to three anuran families, as inhibitors of AChE, BChE and MAO-B enzymes. The extracts also showed antioxidant activities, acting as multi-target on four important pathways of AD.