Bioactivity-guided isolation of leishmanicidal chalcones from Piper delineatum
Leishmaniasis affects approximately 12 million people worldwide, primarily in developing regions . Conventional chemotherapy with pentavalent antimonials is considerably toxic and prone to induce resistance. Second-line drugs, such as amphotericin B and its lipid formulations, are either too toxic or expensive for routine use in developing countries. At the same time, the efficacy of miltefosine against cutaneous leishmaniasis remains to be ascertained [2,3]. Therefore, there is an urgent need to search for novel, effective and safe drugs for the treatment of these diseases .
In our ongoing study of potential leishmanicidal agents from Piper species , we have carried out a bioguided fractionation of the ethanolic extract of the leaves of Piper delineatum Trel. This extract was subsequently partitioned between water and organic solvents of increasing polarity, giving CH2Cl2 and EtOAc fractions. These extracts and the remaining aqueous layer were tested for their leishmanicidal activity against promastigote forms of two strains of Leishmania (L. amazonensis and L. braziliensis). The bioactive CH2Cl2 fraction was subjected to column chromatography, yielding thirteen fractions. The most active fraction (IC50 1.1 and 1.3µg/mL against L. amazonensis and L. braziliensis, respectively) was further subjected to repeat chromatography, affording two new bioactive trans-chalcones: 2',3,4'-trihydroxy-6'-methoxy-chalcone and 2',3,4'-trihydroxy-5,6'-dimethoxy-chalcone, whose structures were elucidated by means of spectrometric and spectroscopic techniques. These results support the use of the Piper species as a traditional remedy in the treatment of parasitic diseases.
Acknowledgement: We are indebted to the Agencia Canaria de Investigación, Innovación y Sociedad de la Información (C200801000049) and RED RAPMA/OPS projects for financial support. TJC is grateful to MAEC-AECID for a fellowship.
References: 1. Report of a meeting of the WHO Expert Committee on the Control of Leishmaniasis (2010). WHO Technical Report Series 949. Switzerland.
2. Griensven J et al. (2010) Lancet Infect Dis.10: 184–194.
3. Bethony J et al. (2011) Immunol Rev 239: 237–270.
4. Nogueira C et al. (2011) Molecules 16: 2146–2190.
5. Parmar V et al. (1997) Phytochemistry 46: 597–673.