title: Bioactivity-guided isolation of laevicarpin, an antitrypanosomal and anticryptococcal lactam from Piper laevicarpu (Piperaceae).
abstract: 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.
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, 09972-270, São Paulo, SP, Brazil.
authors.forename: Dayany
authors.initials: D
authors.lastname: da Silva A Maciel
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, 09972-270, São Paulo, SP, Brazil.
authors.forename: Viviane P
authors.initials: VP
authors.lastname: Freitas
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, 09972-270, São Paulo, SP, Brazil.
authors.forename: Geanne A Alves
authors.initials: GA
authors.lastname: Conserva
authors.affiliation: Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, 01246-000, São Paulo, SP, Brazil.
authors.forename: Tatiana R
authors.initials: TR
authors.lastname: Alexandre
authors.affiliation: Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, 01246-000, São Paulo, SP, Brazil.
authors.forename: Sonia U
authors.initials: SU
authors.lastname: Purisco
authors.affiliation: Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, 01246-000, São Paulo, SP, Brazil.
authors.forename: Andre G
authors.initials: AG
authors.lastname: Tempone
authors.affiliation: Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, 01246-000, São Paulo, SP, Brazil.
authors.forename: Márcia Souza C
authors.initials: MS
authors.lastname: Melhem
authors.affiliation: Instituto de Química, Universidade de São Paulo, 05508-000, São Paulo, SP, Brazil.
authors.forename: Massuo J
authors.initials: MJ
authors.lastname: Kato
authors.affiliation: Instituto de Pesquisas do Jardim Botânico, 22460-030, Rio de Janeiro, RJ, Brazil.
authors.forename: Elsie F
authors.initials: EF
authors.lastname: Guimarães
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, 09972-270, São Paulo, SP, Brazil. Electronic address: joao.lago@unifesp.br.
authors.forename: João Henrique G
authors.initials: JH
authors.lastname: Lago
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D056285:Cryptococcus gattii / Q000187:drug effects; D020128:Inhibitory Concentration 50; D007769:Lactams / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D031701:Piper / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D014344:Trypanocidal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D007769:Lactams; D010936:Plant Extracts; D014344:Trypanocidal Agents; C000613359:laevicarpin
keywords: Cryptococcus gattii; Laevicarpin; Piper laevicarpu; Piperaceae; Trypanosoma cruzi