NEW ANTITUMOR AND/OR ANTI-ANGIOGENIC HETEROCYCLIC COMPOUNDS: SYNTHESIS, MOLECULAR MODELLING AND INHIBITION ENZYMATIC ASSAYS USING TYROSINE KINASE MEMBRANE GROWTH FACTOR RECEPTORS

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Phytochemicals and bioactive properties of Ilex paraguariensis: an in-vitro comparative study between the whole plant, leaves and stems

Publication . Souza, Aloisio Henrique Pereira de; Corrêa, Rúbia C.G.; Barros, Lillian; Calhelha, Ricardo C.; Santos-Buelga, Celestino; Peralta, Rosane M.; Bracht, Adelar; Matsushita, Makoto; Ferreira, Isabel C.F.R.

Leaves, stems and whole plant of Ilex paraguariensis (yerba mate) were characterized in terms of their chemical composition and biological activities in order to determine which part of the plant is more interesting to develop bioactive formulations. The yerba mate samples contain at least five free sugars, five organic acids, eighteen fatty acids, one tocopherol, nine hydroxycinnamoyl derivatives and two flavonols. The leaves extract revealed the highest antioxidant activity, correlating with its highest levels of phenolic compounds. By contrast, the stems extract showed the highest anti-inflammatory potential and was also the most potent against MCF-7 and HepG2 cell lines, probably due to the presence of other phytochemicals. The absence of hepatotoxicity of the extracts was confirmed in porcine liver primary cells. Although the yerba mate extracts have been widely studied, this report shows for the first time the distinct potentialities of each individual part of the plant.

2015Journal article

Open access

Aminodi(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, effects in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of toxicity using non-tumor cells

Publication . Calhelha, Ricardo C.; Ferreira, Isabel C.F.R.; Peixoto, Daniela; Abreu, Rui M.V.; Vale-Silva, Luís A.; Pinto, Eugénia; Lima, Raquel T.; Alvelos, M. Inês; Vasconcelos, M. Helena; Queiroz, Maria João R.P.

Three aminodi(hetero)arylamines were prepared via a palladium-catalyzed C-N Buchwald-Hartwig coupling of methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate with different bromonitrobenzenes, followed by reduction of the nitro groups of the coupling products to the corresponding amino compounds. The aminodi(hetero)arylamines thus obtained were evaluated for their growth inhibitory effect on four human tumor cell lines MCF-7 (breast adenocarcinoma), A375-C5 (melanoma), NCI-H460 (non-small cell lung cancer) and HepG2 (hepatocellular carcinoma). The toxicity to non-tumor cells was also evaluated using a porcine liver primary cell culture (PLP1), established by us. The aminodi(hetero)arylamine with the NH2 group in the ortho position and an OMe group in the para position to the NH of the di(hetero)arylamine, is the most promising compound giving the lowest GI50 values (1.30–1.63 μM) in all the tested human tumor cell lines, presenting no toxicity to PLP1 at those concentrations. The effect of this compound on the cell cycle and induction of apoptosis was analyzed in the NCI-H460 cell line. It was observed that it altered the cell cycle profile causing a decrease in the percentage of cells in the G0/G1 phase and an increase of the apoptosis levels.

2012Journal article

Open access

Antioxidant activity of aminodiarylamines in the thieno[3,2-b]pyridine series: radical scavenging activity, lipid peroxidation inhibition and redox profile

Publication . Calhelha, Ricardo C.; Peixoto, Daniela; Vilas-Boas, Miguel; Queiroz, Maria João R.P.; Ferreira, Isabel C.F.R.

The antioxidant activity of the aminodi(hetero)arylamines, prepared by C-N coupling of the methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate with bromonitrobenzenes and further reduction of the obtained nitro compounds, was evaluated by chemical, biochemical and electrochemical assays. The aminodi(hetero) arylamine with the amino group ortho to the NH and a methoxy group in para, was the most efficient in radical scavenging activity (RSA, 63 mu M) and reducing power (RP, 33 mu M), while the aminodiarylamine with the amino group in para to the NH, gave the best results in beta-carotene-linoleate system (41 mu M) and inhibition of formation of thiobarbituric acid reactive substances in porcine brain cells homogenates (7 mu M), with EC50 values even lower than those obtained for the standard trolox. This diarylamine also presented the lowest oxidation potential, lower than the one of trolox, and the highest antioxidant power in the electrochemical assays. The para substitution with an amino group enables higher antioxidant potential.

2014Journal article

Open access

Infusion and decoction of wild German chamomile: bioactivity and characterization of organic acids and phenolic compounds.

Publication . Guimarães, Rafaela; Barros, Lillian; Dueñas, Montserrat; Calhelha, Ricardo C.; Carvalho, Ana Maria; Santos-Buelga, Celestino; Queiroz, Maria João R.P.; Ferreira, Isabel C.F.R.

Natural products represent a rich source of biologically active compounds and are an example of molecular diversity, with recognized potential in drug discovery. Herein, methanol extract of Matricaria recutita L. (German chamomile) and its decoction and infusion (the most consumed preparations of this herb) were submitted to an analysis of phytochemicals and bioactivity evaluation. The antioxidant activity was determined by free radicals scavenging activity, reducing power and inhibition of lipid peroxidation; the antitumour potential was tested in human tumour cell lines (breast, lung, colon, cervical and hepatocellular carcinomas), and the hepatotoxicity was evaluated using a porcine liver primary cell culture (non-tumour cells). All the samples revealed antioxidant properties. Decoction had no antitumour activity (GI50>400 µg/mL) which could indicate that this bioactivity might be related to compounds (including phenolic compounds) that were not extracted or that were affected by the decoction procedure. Both plant methanol extract and infusion showed inhibitory activity of the growth of HCT-15 (GI50 250.24 and 298.23 µg/mL, respectively) and HeLa (GI50 259.36 and 277.67 µg/mL, respectively) cell lines, without hepatotoxicity (GI50>400 µg/mL). Infusion and decoction gave higher contents of organic acids (24.42 and 23.35 g/100 g dw). Otherwise, the plant methanol extract presented the highest amounts of phenolic acids (3.99 g/100 g dw) and flavonoids (2.59 g/100 g dw). The major compound found in all the preparations was luteolin O-acylhexoside. Overall, German chamomile contains important phytochemicals with bioactive properties (mainly antitumour potential selective to colon and cervical carcinoma cell lines) to be explored in the medicine, food, and cosmetic industries.

2013Journal article

Open access

A detailed comparative study between chemical and bioactive properties of Ganoderma lucidum from different origins

Publication . Stojković, Dejan; Barros, Lillian; Calhelha, Ricardo C.; Glamočlija, Jasmina; Ćirić, Ana; Van Griensven, Leo J.L.D.; Soković, Marina; Ferreira, Isabel C.F.R.

A detailed comparative study on chemical and bioactive properties of wild and cultivated Ganoderma lucidum from Serbia (GS) and China (GCN) was performed. This species was chosen because of their worldwide use as medicinal mushroom. Higher amounts of sugars were found in GS, while higher amounts of organic acids were recorded in GCN. Unsaturated fatty acids predominated over saturated fatty acids. GCN revealed higher antioxidant activity, while GS exhibited inhibitory potential against human breast and cervical carcinoma cell lines. No cytotoxicity in non-tumour liver primary cell culture was observed for the different samples. Both samples possessed antibacterial and antifungal activities, in some cases even better than the standard antimicrobial drugs. This is the first study reporting a comparative of chemical compounds and bioactivity of G. lucidum samples from different origins.

2014Journal article

Open access