Effect of the isocoumarin paepalantine on the luminol and lucigenin amplified chemiluminescence of rat neutrophils

Paepalantine (9,10-dihydroxy-5,7-dimethoxy-1H-naphto(2,3c)pyran-1-one), a natural isocoumarin isolated from the capitula of Paepalanthus bromelioides (Eriocaulaceae), was assessed for its effect on the respiratory burst (zymosan-stimulated luminol-enhanced chemiluminescence and. PMA-stimulated lucigenin-enhanced chemiluminescence) of polymorphonuclear neutrophils in vitro. Special attention was devoted to establishing the IC50 for neutrophils. Paepalantine was able to decrease luminol and lucigenin chemiluminescence, reflecting an inhibitory effect on the respiratory burst, with an ED50 of 0.44 +/- 0.05 and 0.84 +/- 0.15 mug/ml, respectively. A cell-free system was performed with paepalantine on myeloperoxidase/H2O2 and myeloperoxidase/H2O2/Cl- systems. Paepalantine inhibited luminol oxidation in both systems. This inhibition was related to the interaction of paepalantine-myeloperoxidase and its scavenger effect on HOCl.

Evaluation of the genotoxic potential of the isocoumarin paepalantine in in vivo and in vitro mammalian systems

Paepalantine is an isocoumarin isolated from Paepalanthus vellozioides which showed antimicrobial activity in in vitro experiments. In the present study, paepalantine was tested for possible clastogenic and cytotoxic action. Cultures from different individuals were treated with paepalantine at concentrations of 20, 40 and 80 mu g/ml. The effect of isocoumarin was also tested in an in vivo assay using Wistar rat bone marrow cells. Paepalantine was administered intraperitoneally at concentrations of 6.25, 12.5 and 25 mg/kg body weight. Under these conditions paepalantine did not have a clastogenic effect, but was significantly cytotoxic in the in vitro and in vivo mammalian cell systems tested in the present work. (C) 1999 Elsevier B.V. Ireland Ltd. All rights reserved.

Intestinal anti-inflammatory activity of paepalantine, an isocoumarin isolated from the capitula of Paepalanthus bromelioides, in the trinitrobenzenesulphonic acid model of rat colitis

The preventative intestinal anti-inflammatory activity of paepalantine, an isocoumarin isolated from the capitula of Paepalarithus bromelioides, was tested in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. This was performed in two different experimental settings, i. e. when the colonic mucosa is intact or when the mucosa is in process of recovery after an initial insult. The results obtained revealed that the paepalantine pretreatment, at doses of 5 and 10 mg/kg, significantly attenuated the colonic damage induced by TNBS in both situations, as it was evidenced both histologically and biochemically. This beneficial effect was associated with an improvement in the colonic oxidative status, since paepalantine prevented the glutathione depletion that occurred as a consequence of the colonic inflammation. In addition, the intestinal anti-inflammatory effect exerted by this isocoumarin was associated with an inhibition of colonic nitric oxide activity, which is upregulated as a consequence of the inflammatory process. In conclusion, the preventative effect exerted by paepalantine in the TNBS model of rat colitis is probably related with its antioxidant properties.

Mutagenic and cytotoxic activity of an isocoumarin (Paepalantine) isolated from Paepalanthus vellozioides

A new isocoumarin with antimicrobial activity was isolated from Paepalanthus vellozioides (a native Brazilian plant) and called paepalantine. This study was carried out to assess the mutagenic activity of this new agent in assays with Salmonella typhimurium TA100, TA98, and TA102 and in Chinese hamster ovary (CHO) cell cultures, as well as cytotoxicity to McCoy cells. Paepalantine caused a significant dose-dependent increase in the frequency of revertants in the three strains used in the assay, both with and without S9 mix, in concentrations varying from 2 to 128 mu g/ plate. The mutagenicity was confirmed in assays with CHO cells treated in the G(1), S, and G(2) phases of the cell cycle. There was an increase in the chromosomal aberration frequency, mainly in the G(2) phase. Furthermore, the mitotic index of the treated cultures (40,80, and 160 mu g/ml) was significantly lower, indicating cytotoxicity. The midpoint cytotoxicity values to McCoy cells by the neutral red (NR) and microculture tetrazolium (MTT) techniques resulted in a NR50, and MTT50 of 30 and 38 mu g/ml, respectively. Alterations to the paepalantine structure are suggested to reduce its mutagenic and cytotoxic activity in investigations for its antineoplasic potential (C) 1997 Wiley-Liss, Inc.

AN ISOCOUMARIN DERIVATIVE FROM PAEPALANTHUS BROMELIOIDES

The structure of 5,7,9,10-tetramethoxy-3-methyl-1 H-naphtho[2,3-c]pyran-1-one, C18H18O6, a derivative of a natural isocoumarin isolated from Paepalanthus bromelioides, was determined by X-ray analysis, which unequivocally confirmed the previously assigned structure. Small deviations from the standard angles, resulting from steric hindrance between the methoxyl and carbonyl groups, were observed.

Isocoumarin from Paepalanthus bromelioides

The new isocoumarin, 9,10-dihydroxy-5, 7-dimethoxy-1H-naphtho(2,3c)pyran-1-one, was isolated from the capitula of Paepalanthus bromelioides. The structure was established by means of the spectral data of the natural product and its derivatives. The natural isocoumarin isolated has strong antibiotic activity. © 1990.

3-tert-Butyl-1H-isochromene-1-thione

The title compound, C13H14OS, crystallizes with two independent molecules in the asymmetric unit. The unit cell contains three voids of 197 angstrom(3), but the residual electron density (highest peak = 0.24 e angstrom(-3) and deepest hole = -0.18 e angstrom(-3)) in the difference Fourier map suggests no solvent molecule occupies this void. The crystal structure is stabilized by pi-pi interactions between the isocoumarin ring systems, with centroid-centroid distances of 3.6793 (14) and 3.6566 (15) angstrom.

Chemistry in Eriocaulaceae

Eriocaulaceae is a pantropical family that comprises about 1100 species distributed in 11 genera. The infrafamilial relationships are still unsatisfactorily resolved, because of the tiny flowers and generalized morphology, which makes the taxonomy very difficult. Flavonoid and naphthopyranone profiles have proved to be important in order to contribute to the alignment of genera into the family. We here present a survey of the chemical data of Eriocaulaceae with a discussion about their contribution to the taxonomy of Eriocaulaceae.

Mutagenicity of paepalantine dimer and glycoside derivatives from Paepalanthus bromelioides

The first isocoumarin isolated from the methylene chloride extract of Paepalanthus bromelioides, named paepalantine (isocoumarin 1), was found to have antimicrobial activity; but, it is mutagenic clastogenic and cytotoxic. Two other isocoumarins, paepalantine-9-O-beta-D-glucopyranoside (isocoumarin 2) and paepalantine-9-O-beta-D-allopyranosyl(1-->6) glucopyranoside (isocoumarin 3) were isolated from the ethanolic extract. A fourth new isocoumarin, also isolated from the methylene chloride extract of the capitula of P. bromelioides, was characterized as an 8-8' dimer of paepalantine and denominated isocoumarin 4. The abilities of isocoumarins 2, 3 and 4 to induce mutations in Salmonella typhimurium strains TA97a, TA98, TA100 and TA102 were investigated. Mutagenic activity was observed in strain TA97a treated with isocoumarin 2 in the presence of S9 mixture. The substitution of H at position 9 by glucose or glucose-allose caused reductions in the mutagenic activities of paepalantine, indicating this to be an important site for these properties. (C) 2003 Elsevier Ltd. All rights reserved.

Mutagenic and cytotoxic effect of planifolin: A naphthopyranone dimer isolated from Paepalanthus planifolius

A naphthopyranone dimer, named planifolin, was isolated from a methylene chloride extract of the capitula of Paepalanthus planifolius Koern. The molecule (C31H26O10) appeared to be made up of two monomeric portions, semi-vioxanthin and paepalantine (an isocoumarin), linked by an ether bond, and it may possess several kinds of biological activity that can be related to its polyphenolic structure. Short-term tests that detect genetic damage can afford the information needed to evaluate carcinogenic risks of chemicals to humans. The Ames test, recommended for testing the mutagenicity of chemical compounds with potential pharmacological application, was used in the present study. The mutagenic activity was evaluated in Salmonella typhimurium strains TA100, TA98, TA102 and TA97a and the cytotoxic effect in McCoy cells. The in vitro cytotoxicity of planifolin to McCoy cells, tested in microculture with neutral red, showed a significant cytotoxic index (CI50) of 12.83 mu g/mL. Planifolin showed mutagenic activity for TA100, TA98 and TA97a. The results indicate that this new naphthopyranone dimer causes mutations by substitution and by addition and deletion of bases in the sequence of DNA. Moreover, its mutagenic potential was increased by metabolic activation. (c) 2005 Elsevier Ltd. All rights reserved.

In vitro cytotoxicity of some natural and semi-synthetic isocoumarins from Paepalanthus bromelioides

Numerous natural compounds have a potential for therapeutic applications, but may have to be chemically modified to alter toxic side effects. We investigated structural parameters that could affect the cytotoxicity of isocoumarins similar to 9,10-dihydroxy-5,7-dimethoxy-1H-naphtho(2,3c)pyran-1-one (paepalantine 1). Paepalantine 1 has antimicrobial activity, as well as significant in vitro cytotoxic effects in the McCoy cell line. Two other natural and two semi-synthetic isocoumarins with similar structures obtained from the capitula of Paepalanthus bromelioides were tested on the same cell line by the neutral red assay. Substitution of the 9 and/or 10-OH group made these compounds less cytotoxic.

Efeitos sinérgicos da paepalantina, uma isocumarina isolada dos capítulos florais de Paepalanthus bromelioides, sobre a atividade da sulfassalazina no modelo de coliteulcerativa induzida por ácido trinitrobenzenosulfônico em ratos: Patrícia Rodrigues Orsi. -

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)