In vitro Assessment of Camphor Hydrazone Derivatives as an Agent Against Leishmania amazonensis

Due to serious problems with the treatment of leishmaniasis all around the world, here is an urgent need in the search for new drugs that are more effective and safer for the treatment of the various forms of leishmaniasis. Actual therapy is limited and lacks sufficient efficacy due to incomplete elimination of the parasites form of patients. In this sense, we decided to evaluate, by first-time, a series of seventeen camphor hydrazone derivatives (2a-2p) against Leishmania amazonensis.

The compounds previously synthesized from camphor, an abundant natural compound, were evaluated in vitro against the extra and intracellular forms of Leishmania amazonensis, and murine macrophages.

The majority of compounds, fourteen, displayed activity against the intracellular form of the parasite (amastigote) with IC₅₀ values ranging from 21.78 to 58.23 µM, being six compounds active for both forms of the parasite. The compound 2i exhibited higher activity against the amastigote form with the value of IC₅₀ (21.78 µM) close to standard utilized miltefosine (12.74 µM) and selectivity index of at least 6.9. Six compounds displayed activity against promastigote form of Leishmania amazonensis 2g, 2j-2n (41.17-69.59 µM), with the compound 2m being the more active with IC₅₀ = 41.17 µM, 1.9 times less active than the reference drug (IC₅₀ = 21.39 µM). The compound 2m was the more selective to this form, with a selectivity index of at least 3.6. All the compounds were non-cytotoxic to macrophages.

Most compounds showed activity against amastigote form of Leishmania amazonensis, being that they were not cytotoxic to macrophage at the maximum tested concentration, showing the selective property of these compounds. Since amastigotes are the parasite stages that cause the disease in humans, these results highlight the antileishmanial effect of the compounds. This study indicates the possible development of candidates to leishmanicidal drugs from an abundant natural compound of easy access.