Effect of 3‐Alkylpyridine Marine Alkaloid Analogues in Leishmania Species Related to American Cutaneous Leishmaniasis

Abstract

These authors contributed equally in this work.A series of oxygenated analogues of marine 3-alkylpyridine alkaloids were synthesized, and their leishmanicidal activity was assayed. All compounds were prepared from 3-pyridinepropanol in few steps and in good yields. The key step for the synthesis of these compounds was a classic Williamson etherification under phase-transfer conditions. Besides toxicity in peritoneal macrophages, the compounds exhibited a significant leishmanicidal activity. Of twelve compounds tested, five showed a strong leishmanicidal activity against promastigote forms of Leishmania amazonensis and L. braziliensis with IC 50 below 10 lM. Compounds 11, 14, 15, and 16 showed a strong leishmanicidal activity on intracellular amastigotes (IC 50 values of 2.78; 0.27; 1.03, and 1.33 lM, respectively), which is unlikely to be owing to the activation of nitric oxide production by macrophages.

Synthesis, antileishmanial activity and QSAR studies of 2-chloro- N -arylacetamides

“…Therefore, the search for new cheap, potent and safe therapeutic alternatives is needed and has been pursued by several groups (Birhan, Bekhit, Hymete, 2014;Coimbra et al, 2013;Gómez-Pérez et al, 2014;Bonano et al, 2014;Gellis et al, 2012;Machado et al, 2012).…”

In vitro evaluation of the schistosomicidal effect of the extracts, fractions and major 3-hydroxy-2,6-dialkyl-substituted piperidine alkaloids from the flowers of Senna spectabilis (Fabaceae)

“…In this same context, another recent study showed that 3alkylpyridine marine alkaloid analogues showed significant toxicity against murine peritoneal macrophages. 55 Regarding to PZQ security index, it was conducted tests until the concentration of 500.0 lg/mL, but no toxicity was observed at murine macrophages (data not shown).…”

Recent Developments in Drug Discovery for Leishmaniasis and Human African Trypanosomiasis

“…A small set of synthesized pyridinium salts ( 64 ) (Figure 12 ), similar in structure to the bioactive marine natural products viscosaline and theonelladin C, were found to be only moderately active against L. amazonensis and L. braziliensis promastigotes; however, they were remarkably specific against the intracellular form of the parasite. 196 Similarly, an antileishmanial screen of synthetic derivatives of the bioactive natural product agelasine D led to the discovery of two potent imidazolium compounds 65 and 66 with EC 50 values of 0.09 and <0.11 μg/mL, respectively, against L. infantum intracellular amastigotes. 197 …”