Luciana G. S. Souza

A novel o-naphtoquinone inhibits N-cadherin expression and blocks melanoma cell invasion via AKT signaling

The down-regulation or loss of epithelial markers is often accompanied by the up-regulation of mesenchymal markers. E-cadherin generally suppresses invasiveness, whereas N-cadherin promotes invasion and metastasis in vitro. The aim of this work is to investigate the role of biflorin, a naphthoquinone with proven anticancer properties, on the expression of N-cadherin and AKT proteins in MDA-MB-435 invasive melanoma cancer cells after 12h of exposure to 1, 2.5 and 5 μM biflorin. Biflorin inhibited MDA-MB-435 invasion in a dose-dependent manner (p<0.01). Likewise, biflorin down-regulated N-cadherin and AKT-1 expression in a dose-dependent manner. Biflorin did not inhibit the adhesion of MDA-MB-435 cells to any tested substrates. Additionally, biflorin blocked the invasiveness of cells by down-regulating N-cadherin, most likely via AKT-1 signaling. As such, biflorin may be a novel anticancer agent and a new prototype for drug design.

Inhibition of metastatic potential of B16-F10 melanoma cell line in vivo and in vitro by biflorin

AIM The aim of this study was to determine the antimetastatic potential of biflorin using in vivo and in vitro approaches. MAIN METHODS Biflorin was isolated from Capraria biflora collected in Fortaleza, Ceará, Brazil. Adhesion, migration and invasion assays were performed to avail of the antimetastatic potential of this quinone. Experimental metastasis was performed to avail of the antimetastatic potential of bilflorin using in vivo assay. KEY FINDINGS Treatment with biflorin (25 and 50mg/kg/day) was shown to be effective in reducing B16-F10 melanoma metastasis in C57BL/6 mice. The administration of biflorin at 25mg/kg/day intraperitoneally inhibited the formation of metastases by about 57% compared to untreated control animals. When the animals were treated with 50mg/kg/day intraperitoneally, there was a 71% decrease in the number of lung metastases. Morphological assays showed the presence of hemosiderin and erythrocytes in the lung parenchyma, indicating the occurrence of hemorrhage, probably a side effect of biflorin. Biflorin at non-toxic concentrations (0.5, 1.0 and 1.5g/mL) was tested directly on B16-F10 cells in vitro, and it inhibited cell adhesion to type I collagen and cell motility using the wound-healing assay. SIGNIFICANCE These data suggest that biflorin has a promising antimetastatic potential, as shown by its anti-adhesion, anti-migration and anti-invasion properties against a metastatic melanoma cell line. However, further studies are essential to elucidate its mechanism of action.

Synthesis, antibacterial and cytotoxic activities of new biflorin-based hydrazones and oximes.

Biflorin 1 is a biologically active quinone, isolated from Capraria biflora. Five new biflorin-based nitrogen derivatives were synthesized, of which two were mixtures of (E)- and (Z)- isomers: (Z)-2a, (Z)-2b, (Z)-3a, (Z)- and (E)-3b, (Z)- and (E)-3c. The antibacterial activity was investigated using the microdilution method for determining the minimum inhibitory concentration (MIC) against six bacterial strains. Tests have shown that these derivatives have potential against all bacterial strains. The cytotoxic activity was also evaluated against three strains of cancer cells, but none of the derivatives showed activity.

Biflorin: an o-naphthoquinone of clinical significance

Biflorin is an o-naphthoquinone with proven cytotoxic effects on tumor cells showing antimicrobial, antitumor and antimutagenic activities. Biflorin is an isolated compound taken from the roots of the plant Capraria biflora L. (Schrophulariaceae), indigenous of the West Indies and South America, which is located in temperate or tropical areas. This compound has shown to be strongly active against grampositive and alcohol-acid-resistant bacteria. It has been efficient in inhibiting the proliferation tumor cell lines CEM, HL-60, B16, HCT-8 and MCF-7. Recently, SK-Br3 cell line was treated with biflorin showing important cytotoxic effects. In this article, information related to the first structural characterization studies are presented, as well as the latest reports concerning the biological activity of this molecule.

Chemical composition of the essential oil and fixed oil Bauhinia pentandra (Bong.) D. Dietr.

Background: Bauhinia pentandrais popularly known as “mororó” and inhabits the Caatinga and Savannah biomes. Objective: This paper reports the chemical composition of the essential and fatty oils of the leaves from B. pentandra. Materials and Methods: The essential oil was obtained by hydrodistillation and the fixed oil by extraction with hexane, followed by saponification with KOH/MeOH, and methylation using MeOH/HCl. The constituents were analyzed by gas chromatography-mass spectrometry. Results: The major constituent of the essential oil was the phytol (58.78% ±8.51%), and of the fatty oil were palmitic (29.03%), stearic (28.58%) and linolenic (10.53%) acids. Conclusion: Of the compounds identified in the essential oil, three are first reported in this species, and this is the first record of the chemical composition of the fixed oil.

SYNTHESIS, LARVICIDAL AND ACETYLCHOLINESTERASE INHIBITORY ACTIVITIES OF CARVACROL/THYMOL AND DERIVATIVES

Bruna M. de Mesquitaa, Patricia G. G. do Nascimentoa, Luciana G. S. Souzaa, Iolanda F. de Fariasa, Romézio A. C. da Silvaa, Telma L. G. de Lemosa,*, Francisco J. Q. Montea, Irvila R. Oliveiraa, Maria T. S. Trevisana, Horlando C. da Silvaa and Gilvandete M. P. Santiagob Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Campus do Pici, 60021-940 Fortaleza – CE, Brasil Departamento de Farmácia, Universidade Federal do Ceará, Campus Porangabussu, 60430-370 Fortaleza – CE, Brasil

Withanolides from Leaves of Nicandra physalodes

Five new withanolides, designated as 15-oxo-nicaphysalin B, 6β,7α-dihydroxynicandrenone 10, 24α,25β-dihydroxy-nicandrenone-2 and a mixture of the epimers 17-(1α/1β-methylpropanone)nicandrenone, in addition to six known others, were isolated from the leaf acetone extract from Nicandra physalodes. The complete structures of the five new withanolides, particularly their relative stereochemistries, were established by extensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HRESIMS). The main isolated withanolides were evaluated for their antibacterial, antifungal and larvicidal properties, but, except nicandrenone, which showed marginal larvicidal activity, none of them was active.

7-epi-griffonilide, a new lactone from Bauhinia pentandra: complete 1H and 13C chemical shift assignments

A new lactone, 7-epi-griffonilide (1), and six known compounds, 2, 3a - 3c, 4a and 4b, were isolated from the leaves of Bauhinia pentandra (Fabaceae). The structures elucidation of 1 and 2 were based on detailed 2D NMR techniques and spectral comparison with related compounds, leading to complete assignment of the 1H and 13C NMR spectra.

Biflorin induces cytotoxicity by DNA interaction in genetically different human melanoma cell lines.

Cancer is a public health problem and the second leading cause of death worldwide. The incidence of cutaneous melanoma has been notably increasing, resulting in high aggressiveness and poor survival rates. Taking into account the antitumor activity of biflorin, a substance isolated from Capraria biflora L. roots that is cytotoxic in vitro and in vivo, this study aimed to demonstrate the action of biflorin against three established human melanoma cell lines that recapitulate the molecular landscape of the disease in terms of genetic alterations and mutations, such as the TP53, NRAS and BRAF genes. The results presented here indicate that biflorin reduces the viability of melanoma cell lines by DNA interactions. Biflorin causes single and double DNA strand breaks, consequently inhibiting cell cycle progression, replication and DNA repair and promoting apoptosis. Our data suggest that biflorin could be considered as a future therapeutic option for managing melanoma.

New Epimeric Spirostanol and Furostanol-Type Steroidal Saponins from Cestrum laevigatum L.

Four new epimeric spirostanol and furostanol-type steroidal saponins, (25R,S)-5α-spirostan2α,3β-diol 3-O-β-D-glucopyranosyl-(1→4)-β-D-galactopyranosyl-(1→4)-β-D-galactopyranoside, (25R,S)-5α-spirostan-2α,3β-diol 3-O-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→4)β-D-galactopyranoside, 26-O-β-D-glucopyranosyl-(25R,S)-5α-furost-20-ene,2α,3β-diol 3-O-β-Dgalactopyranoside and 26-O-β-D-glucopyranosyl-(25R,S)-5α-furost-20-ene,2α,3β-diol 3-O-β-Dgalactopyranosyl-(1→4)-β-D-galactopyranoside, in addition to the known (25R,S)-5α-spirostan2α,3β-diol 3-O-β-D-galactopyranoside, were isolated from Cestrum laevigatum. Compounds were submitted to cytotoxic activity assays using colorectal adenocarcinoma (HCT-116), human promyelocytic leukemia (HL-60), ovarian carcinoma (OVCAR-8), glioma (SF-295) human cancer cell lines, and the antimicrobial activity was evaluated against Candida parapsilosis, C. albicans, C. krusei, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis.