**4. Dermaseptins and Anticancer Therapy**

#### *4.1. Dermaseptins*

Dermaseptins (DRSs) are a class of peptides identified in the skin secretions of several Amazonian tree frogs of the family *Phyllomedusidae*, in particular, the species *Phyllomedusa* [70,71]. The first member of DRS family was isolated from the skin secretion of *P. sauvagei* and named DRS-S1 [72]. This 34-residues-containing peptide has antimicrobial activity against Gram-positive and Gram-negative bacteria, yeast and protozoa without affecting mammalian cells. The second is DRS-B2, isolated from exudates of *P. bicolor* [73–75]. It is also known as adenoregulin due to its capacity to increase the affinity of the agonist toward the receptor of adenosine A1 [76]. DRS-B2, with its 33 amino-acid residues, is considered the most abundant member and the most active peptide of the B family (B for the frog species *P. bicolor*). To date, more than 65 DRSs, listed in the APD3 database (https://aps.unmc.edu/, accessed on 1 June 2022) [26], have been isolated primarily from the skin secretion of South American tree frogs of the 67-member family *Phyllomedusidae* (https://amphibiansoftheworld.amnh.org/, accessed on 1 June 2022). Multiple alignments of the 67 sequences of DRSs listed in APD3 clearly showed that these polycationic peptides, rich in Lys residue, share a signature consisting of a conserved Trp residue at position three and a consensus AA(A/G)KAAL(G/N)A motif in the middle region [70]. Their MIC values are in the low micromolar range for a large panel of microorganisms, comprising bacteria (*S. aureus*, *E. coli*), yeast (*C. albicans*), filamentous fungi (*A. fumigatus*) and protozoa, such as *Leishmania Mexicana*, and show no hemolytic activity against human and rabbit erythrocytes. The mode of action by which DRSs kill these microorganisms follows the "carpet" mechanism [77,78]. These polycationic peptides, destructured in aqueous media, adopt an alpha helix structure upon contact with the host cell plasma membranes and then interact with their negative charges [79–82]. Once bound, the peptide will disrupt membrane permeability and cause the death of the microorganism (Figure 1).
