The bioactivity guided fractionation of the dichloromethane extract of Mitracarpus frigidus afforded the pyranonaphthoquinone psychorubrin. This compound, hitherto unknown in the genus Mitracarpus, had its biological activity evaluated against one panel of bacteria and two fungi, three tumor cell lines (HL60, Jurkat and MCF-7) and four Leishmania species. Its identity was confirmed unambiguously by 1 H, 13 C, 1 H-COSY, IR and UV-Vis spectroscopy and mass spectrometry. Psychorubrin displayed a very promising antitumor with IC 50 of 4.5, 5.6 and 1.1 µM for HL60, Jurkat and MCF-7 cell lines, respectively. Antimicrobial activity, mainly against Cryptococcus neoformans (MIC of 87.3 µM) was observed. A pronounced antileishmanial potential was also verified with IC 50 varying from 1.7 to 2.7 µM for the Leishmania species tested. This is the first report of the presence of pyranonapthoquinones in the Mitracarpus genus, which may serve as a chemotaxonomical marker.

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.

No abstract