Bio-guided isolation of leishmanicidal and trypanocidal constituents from Pituranthos battandieri aerial parts

Abstract

Protozoan pathogens that cause neglected tropical diseases are a major public health concern in tropical and developing countries. In the course of our ongoing search for new lead compounds as potential antiprotozoal agents, this study aims to perform a bio-guided fractionation of Pituranthos battandieri, using an in vitro assay against Leishmania amazonensis and Trypanosoma cruzi. Two known polyacetylenes, (ð€€€ )-panaxydiol (1) and (ð€€€ )-falcarindiol (2) were identified from the ethanolic extract of the aerial parts of P. battandieri as the main bioactive constituents. Compounds 1 and 2 showed similar potency (IC50 values of 5.76 and 5.68 μM, respectively) against L. amazonensis to miltefosine (IC50 value of 6.48 μM), the reference drug, and low toxicity on macrophage cell lines J774. Moreover, compound 1 exhibited moderate activity (IC50 23.24 μM) against T. cruzi. In addition, three known furanocoumarins, 8-geranyloxypsoralen (3), 8-geranyloxy-5-methoxypsoralen (4), and phellopterin (5) were isolated. Their structures were elucidated by NMR and MS analysis. Compounds 1 and 2 are described for the first time in the Pituranthos genus, and this is the first report on their antiprotozoal activity. These results highlight this type of polyacetylenes as an interesting scaffold for the development of novel antiparasitic drugs.