Bioactivity-guided isolation of laevicarpin, an antitrypanosomal and anticryptococcal lactam from Piper laevicarpu (Piperaceae)

• Published in: Fitoterapia 2016-06, Vol.111, p.24-28
• Main Authors: da Silva A. Maciel, Dayany, Freitas, Viviane P., Conserva, Geanne A. Alves, Alexandre, Tatiana R., Purisco, Sonia U., Tempone, Andre G., Melhem, Márcia Souza C., Kato, Massuo J., Guimarães, Elsie F., Lago, João Henrique G.
• Format: Article
• Language: English
• Subjects: Cryptococcus gattii; Laevicarpin; Piper laevicarpu; Piperaceae; Trypanosoma cruzi
• ISSN: 0367-326X
• DOI: 10.1016/j.fitote.2016.04.005

Crude CH2Cl2 extract from leaves of Piper laevicarpu (Piperaceae) displayed antitrypanosomal activity against trypomastigote forms of Trypanosoma cruzi (Y strain) and antimicrobial potential against Cryptococcus gattii (strain-type WM 178). Bioactivity-guided fractionation of crude extract afforded one new natural bioactive lactam derivative, named laevicarpin. The structure of isolated compound, which displayed a very rare ring system, was elucidated based on NMR, IR and MS spectral analysis. Using MTT assay, the trypomastigotes of T. cruzi demonstrated susceptibility to laevicarpin displaying IC50 value of 14.7μg/mL (49.6μM), about 10-fold more potent than the standard drug benznidazole. The mammalian cytotoxicity of laevicarpin was verified against murine fibroblasts (NCTC cells) and demonstrated a CC50 value of 100.3μg/mL (337.7μM–SI=7). When tested against Cryptococcus gattii, laevicarpin showed an IC50 value of 2.3μg/mL (7.9μM) and a MIC value of 7.4μg/mL (25μM). Based in the obtained results, laevicarpin could be used as a scaffold for future drug design studies against the Chagas disease and anti-cryptococosis agents. [Display omitted]