Investigation of synergy between existing antileishmanial agents and novel candidate compounds in Cutaneous Leishmaniasis

This study was carried out to determine the antileishmanial activities of existing antileishmanial agents and new candidate compounds against Leishmania tropica promastigotes and to examine the synergistic interaction between conventional antileishmanial agents and essential oil components or antibiotics. While the activities of essential oil components, antibiotics and antileishmanial agents against L. tropica promastigotes were determined by microdilution method with RPMI 1640, the checkerboard method was used in synergy studies. L. tropica (MHOM/AZ/1974/SAF-K27) promastigotes obtained from Parasite Bank in Dept. of Medical Parasitology of Manisa Celal Bayar University were used in this study, Antileishmanial agents, meglumine antimoniate (Glucantime®), sodium stibogluconate (Pentostam®), paromomycin, miltefosine and amphotericin B, antibiotics (tetracycline, tigecycline, clindamycin) and essential oil components (carvacrol, thymol) were selected and included in the study.Although the antibacterial effect of the efflux pump inhibitors alone were not strong, the interaction with the antibiotics tested was mostly synergistic or additive. It has been shown that antileishmanial agents, sodium stibogluconate, miltefosine and amphotericin B and all antibiotics tested have strong activity, paromomycin weak activity. Combinations of all tested antibiotics with sodium stibogluconate, miltefosine and amphotericin B showed synergistic effects, while the essential oil components tested did not show a synergistic effect with any of the antileishmanial agents. In conclusion, the demonstration of synergistic interactions between antileishmanial agents and antibiotics in clinical use has the potential to reduce the dose and duration of treatment of these agents (especially amphotericin B).