title: Cytotoxic non-aromatic B-ring flavanones from Piper carniconnectivum C. DC.
abstract: The EtOAc extract from the leaves of Piper carniconnectivum C. DC. was subjected to chromatographic separation to afford two non-aromatic B-ring flavanone compounds: 5-hydroxy-2-(1'-hydroxy-4'-oxo-cyclohex-2'-en-1'-yl)-6,7-dimethoxy-2,3-dihydro-4H-chromen-4-one (1) and 5-hydroxy-2-(1',2'-dihydroxy-4'-oxo-cyclohexyl)-6,7-dimethoxy-2,3-dihydro-4H-chromen-4-one (2). The absolute configuration of (+)-1 was unambiguously determined as 2S,1'R by electronic circular dichroism (ECD) spectroscopy and comparison to simulated spectra that were calculated using time-dependent density functional theory (TDDFT). This methodology allowed the assignment of the absolute configuration of (+)-2 also as 2S,1'R, except for the stereogenic center at C-2', which was assigned as R because of the evidence drawn from high resolution NMR experiments. The cytotoxic activity of both compounds and 3 (hydrogenated B-ring derivative of 1) was evaluated on twelve human leukemia cell lines, and the IC50 values (<10 μM) indicated the activity of 1 against seven cell lines.
authors.affiliation: Research Support Center in Molecular Diversity of Natural Products, Instituto de Química, Universidade de São Paulo, CP 26077, 05599-970 São Paulo, SP, Brazil.
authors.forename: Giovana C
authors.initials: GC
authors.lastname: Freitas
authors.affiliation: NUBBE, Instituto de Química, Universidade Estadual Paulista, UNESP, 14800-900 Araraquara, SP, Brazil.
authors.forename: João M
authors.initials: JM
authors.lastname: Batista
authors.affiliation: Centro Integrado de Pesquisas Oncohematológicas na Infância, UNICAMP, CP 6141, 13083-970 Campinas, SP, Brazil.
authors.forename: Gilberto C
authors.initials: GC
authors.lastname: Franchi
authors.affiliation: Centro Integrado de Pesquisas Oncohematológicas na Infância, UNICAMP, CP 6141, 13083-970 Campinas, SP, Brazil.
authors.forename: Alexandre E
authors.initials: AE
authors.lastname: Nowill
authors.affiliation: Research Support Center in Molecular Diversity of Natural Products, Instituto de Química, Universidade de São Paulo, CP 26077, 05599-970 São Paulo, SP, Brazil.
authors.forename: Lydia F
authors.initials: LF
authors.lastname: Yamaguchi
authors.affiliation: Research Support Center in Molecular Diversity of Natural Products, Instituto de Química, Universidade de São Paulo, CP 26077, 05599-970 São Paulo, SP, Brazil.
authors.forename: Janaina D
authors.initials: JD
authors.lastname: Vilcachagua
authors.affiliation: Research Support Center in Molecular Diversity of Natural Products, Instituto de Química, Universidade de São Paulo, CP 26077, 05599-970 São Paulo, SP, Brazil.
authors.forename: Denize C
authors.initials: DC
authors.lastname: Favaro
authors.affiliation: NUBBE, Instituto de Química, Universidade Estadual Paulista, UNESP, 14800-900 Araraquara, SP, Brazil.
authors.forename: Maysa
authors.initials: M
authors.lastname: Furlan
authors.affiliation: Instituto de Pesquisas Jardim Botânico do Rio de Janeiro, Rua Pacheco Leão 2040, 22460-030 Rio de Janeiro, RJ, Brazil.
authors.forename: Elsie F
authors.initials: EF
authors.lastname: Guimarães
authors.affiliation: Department of Chemistry, University of Nevada, Reno, NV 89557, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Jeffrey
authors.affiliation: Research Support Center in Molecular Diversity of Natural Products, Instituto de Química, Universidade de São Paulo, CP 26077, 05599-970 São Paulo, SP, Brazil. Electronic address: majokato@iq.usp.br.
authors.forename: Massuo J
authors.initials: MJ
authors.lastname: Kato
mesh_terms: D002942:Circular Dichroism; D004354:Drug Screening Assays, Antitumor; D044950:Flavanones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D019906:Nuclear Magnetic Resonance, Biomolecular; D031701:Piper / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: C000588791:5-hydroxy-2-(1',2'-dihydroxy-4'-oxo-cyclohexyl)-6,7-dimethoxy-2,3-dihydro-4H-chromen-4-one; C000588790:5-hydroxy-2-(1'-hydroxy-4'-oxo-cyclohex-2'-en-1'-yl)-6,7-dimethoxy-2,3-dihydro-4H-chromen-4-one; D044950:Flavanones
keywords: Cytotoxic; Non-aromatic B-ring flavanone; Piper carniconnectivum; Piperaceae