Bioactive Secolignans from Peperomia dindygulensis

Abstract

Thirteen secolignans, including eight new ones (1-8), were isolated from the EtOAc extract of Peperomia dindygulensis. The structures were mainly elucidated by 1D and 2D NMR and MS experiments, the relative configurations were determined by NOE correlations, and the absolute configurations were established by the optical rotations and CD spectra. Cytotoxicity and MDR (multidrug resistance) reversal activity of the isolated compounds were examined. Compounds 6 and 7, peperomins B (10) and E (12), showed moderate to strong growth inhibitory activity against a malignant lung tumor cell (VA-13) with IC(50) values of 15.2, 13.5, 13.9, and 1.93 microM, respectively, and also inhibited the growth of a normal lung fibroblast cell (WI-38) at the same levels. Compound 7 and peperomin E (12) exhibited inhibitory activity against a liver tumor cell (HepG2) with IC(50) values of 22.3 and 12.1 microM. Compounds 5 and 7 and peperomins A, B, C, and E (9-12) enhanced calcein accumulation in MDR 2780 cells at 25 microg/mL. Compounds 2, 3, 7, and peperomin E (12) showed inhibitory activity on induction of the intercellular adhesion molecule-1 (ICAM-1).

Chemical biology of inflammatory cytokine signaling

“…Recently, we have reported that several secolignans isolated from the extract of Peperomia dindygulensis inhibit cell-surface ICAM-1 expression induced by pro-inflammatory cytokines. 81 However, except for their anti-inflammatory activity, 81 multidrug resistance reversal activity 81 and anticancer activity, 81,82 the biological activities of peperomins are little understood. Peperomin E and 2,6-didehydropeperomin B (Figure 4) are structural analogs of peperomin A and peperomin B in which the a-methylene-g-lactone groups are replaced with a-methyl-g-lactone groups, respectively.…”

Chemistry and evolution of the Piperaceae

“…Among the few examples that have been reported are the isolation of an antitumor dibenzylbutyrolactone derivative [43,44], and tetrahydrofuran lignans [45]. Several tetrahydrofuran lignans have also been isolated from Piper solmsianum, and these exhibit potent in vitro trypanocidal activities against trypomastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease [46].…”

“…Some structurally related compounds from Peperomia, including prenylated phenolics [16] and polyketide-chromenes [17,18], have been reported. Additionally, compounds derived from the shikimate pathway are also well represented in Peperomia species and these include the secolignans, the peperomins, and the styrene dimers derived from phenylpropanoid in which the γ-carbon is absent [19,20].…”

Bioprospecção em espécies de Piperaceae

“…Entre as espécies estudadas, podem ser citadas Peperomia proctorii (Seeram et al, 2000), Peperomia galiodes (Mahiou et al, 1995), Peperomia dindigulensis (Govindachari et al, 1998;Wu et al, 2006), Peperomia pellucida (Xu et al, 2006) e Peperomia villipetiola (Salazar et al, 2005).…”

“…As peperominas A (17) e E (18) encontram-se descritas na literatura, com registros de atividade antifágica frente a Spodoptera litura, Rhaphidopalpa foveicollis e Atractomorpha crenulata (Govindachari et al, 1998) e anti-tumoral (células VA-13 e HepG2) (Wu et al, 2006). Entretanto, não há nenhum relato sobre o potencial antifúngico destas substâncias.…”