*7.2. Lipopeptide PAL-Lys-Lys-NH2*

The short lipopeptide palmitoyl PAL-Lys-Lys-NH2 (PAL) was evaluated in vitro against *Candida* spp. alone and in combination with fluconazole, amphotericin B, and caspofungin. All drugs showed good activity against *Candida* strains; however amphotericin B and caspofungin had the lowest MIC. PAL showed relevant synergistic action with PAL/fluconazole (81.25%), PAL/amphotericin B (75%), and particularly with PAL/caspofungin (87.5%) [90]. In our opinion, the combination of PAL/caspofungin may be a new therapeutic option in cases of severe candida infection.

In cases of severe *Cryptococcus neoformans* infections, PAL was also effective in vitro, showing synergy in 21.4% of cases with amphotericin B, suggesting its possible use in infected patients to reduce the dosage and side effects of amphotericin B [91].

PAL was also studied in vitro against several clinical isolates of *dermatophytes* [92,93]. PAL and fluconazole showed a lower MIC and lower fungal biomass than gamma-terpinene, a component of tea tree oil. Finally, PAL was superior to fluconazole in reducing hyphal viability against both dermatophytes, suggesting its possible role in the treatment of these fungi as well.
