Synthesis of new potential biological active compounds based on thiophene fused N-heterocycle scaffolds using cross-couplings, C-H activation and intra/intermolecular cyclizations Título antigo: Synthesis of new potential biological active compounds based on thiophene fused N-heterocycle scaffolds using cross-couplings, C-H activation and intramolecular cyclizations

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Magnetoliposomes based on magnetic/plasmonic nanoparticles loaded with tricyclic lactones for combined cancer therapy

Publication . Rio, Irina S.R.; Rodrigues, Ana Rita O.; Rodrigues, Juliana M.; Queiroz, Maria João R.P.; Calhelha, Ricardo C.; Ferreira, Isabel C.F.R.; Almeida, Bernardo G.; Pires, Ana; Pereira, André M.; Araújo, João Paulo; Castanheira, Elisabete M.S.; Coutinho, Paulo J.G.

Liposome-like nanoarchitectures containing manganese ferrite nanoparticles covered or decorated with gold were developed for application in dual cancer therapy, combining chemotherapy and photothermia. The magnetic/plasmonic nanoparticles were characterized using XRD, UV/Visible absorption, HR-TEM, and SQUID, exhibiting superparamagnetic behavior at room temperature. The average size of the gold-decorated nanoparticles was 26.7 nm for MnFe2 O4 with 5–7 nm gold nanospheres. The average size of the core/shell nanoparticles was 28.8 nm for the magnetic core and around 4 nm for the gold shell. Two new potential antitumor fluorescent drugs, tricyclic lactones derivatives of thienopyridine, were loaded in these nanosystems with very high encapsulation efficiencies (higher than 98%). Assays in human tumor cell lines demonstrate that the nanocarriers do not release the antitumor compounds in the absence of irradiation. Moreover, the nanosystems do not cause any effect on the growth of primary (non-tumor) cells (with or without irradiation). The drug-loaded systems containing the core/shell magnetic/plasmonic nanoparticles efficiently inhibit the growth of tumor cells when irradiated with red light, making them suitable for a triggered release promoted by irradiation.

2021Journal article

Open access

Synthesis of novel methyl 7-[(Hetero)arylamino]thieno[2,3-b] pyrazine-6-carboxylates and antitumor activity evaluation: effects in human tumor cells growth, cell cycle analysis, apoptosis and toxicity in non-tumor cells

Publication . Rodrigues, Juliana M.; Calhelha, Ricardo C.; Nogueira, António José M.; Ferreira, Isabel C.F.R.; Barros, Lillian; Queiroz, Maria João R.P.

Several novel methyl 7-[(hetero)arylamino]thieno[2,3-b]pyrazine-6-carboxylates were synthe-sized by Pd-catalyzed C–N Buchwald–Hartwig cross-coupling of either methyl 7-aminothieno[3,2-b] pyrazine-6-carboxylate with (hetero)arylhalides or 7-bromothieno[2,3-b]pyrazine-6-carboxylate with (hetero)arylamines in good-to-excellent yields (50% quantitative yield), using different reaction conditions, namely ligands and solvents, due to the different electronic character of the substrates. The antitumoral potential of these compounds was evaluated in four human tumor cell lines: gastric adenocarcinoma (AGS), colorectal adenocarcinoma (CaCo-2), breast carcinoma (MCF7), and non-small-cell lung carcinoma (NCI-H460) using the SRB assay, and it was possible to establish some structure–activity relationships. Furthermore, they did not show relevant toxicity against a non-tumor cell line culture from the African green monkey kidney (Vero). The most promising compounds (GI50 ≤ 11 µM), showed some selectivity either against AGS or CaCo-2 cell lines without toxicity at their GI50 values. The effects of the methoxylated compounds 2b (2-OMeC6 H4 ), 2f and 2g (3,4-or 3,5-diOMeC6 H3, respectively) on the cell cycle profile and induction of apoptosis were further studied in the AGS cell line. Nevertheless, even for the most active (GI50 = 7.8 µM) and selective compound (2g) against this cell line, it was observed that a huge number of dead cells gave rise to an atypical distribution on the cell cycle profile and that these cells were not apoptotic, which points to a different mechanism of action for the AGS cell growth inhibition.

2021Journal article

Open access