Synthesis of Tricyclic and Tetracyclic Lactone Derivatives of Thieno[2,3-]pyrazine or Thieno[2,3-]quinoline: Preliminary Antitumor and Antiparasitic Activity Evaluation.

Tricyclic and tetracyclic lactone derivatives of thieno[2,3-]pyrazine or thieno[2,3-]quinoline, and 2-pyrones were prepared using different methodologies. Pd/Cu-catalyzed Sonogashira coupling using EtN as a base, of methyl 7-bromothieno[2,3-]pyrazine-6-carboxylate and (het)arylalkynes to yield the Sonogashira ester products, gave also the corresponding tricyclic lactones as minor products. However, the major products did not cyclize with TFA.

Synthesis of - and ,-Heterocycle-Dipeptide Conjugates for Supramolecular Hydrogel Formation.

Small peptides with aromatic nuclei at the -terminus have been shown to form bioactive, biocompatible, and biodegradable supramolecular peptide hydrogels. Novel heterocycle-dipeptide conjugates with potential biological activity or application as drug carriers were synthesized by using (benzo[]thiophene) and ,(thieno [2,3-]pyridine and thieno[2,3-]quinoline) heterocycles as -protective groups for dipeptides l-Phe-l-Phe and l-Phe-l-Leu. The synthesis involved coupling heterocyclic carboxylic acids with trifluoroacetate salts of ethyl l-phenylalanyl-l-phenylalaninate and ethyl l-phenylalanyl- l-leucinate using HBTU and EtN, producing the corresponding six -heterocycle-dipeptide ester conjugates, which were then hydrolyzed to the carboxylic acids.

Magnetoliposomes Containing Multicore Nanoparticles and a New Antitumor Thienopyridine Compound with Potential Application in Chemo/Thermotherapy.

Multicore magnetic nanoparticles of manganese ferrite were prepared using carboxymethyl dextran as an agglutinating compound or by an innovative method using melamine as a cross-coupling agent. The nanoparticles prepared using melamine exhibited a flower-shape structure, a saturation magnetization of 6.16 emu/g and good capabilities for magnetic hyperthermia, with a specific absorption rate (SAR) of 0.

Development of Thermo- and pH-Sensitive Liposomal Magnetic Carriers for New Potential Antitumor Thienopyridine Derivatives.

The development of stimuli-sensitive drug delivery systems is a very attractive area of current research in cancer therapy. The deep knowledge on the microenvironment of tumors has supported the progress of nanosystems' ability for controlled and local fusion as well as drug release. Temperature and pH are two of the most promising triggers in the development of sensitive formulations to improve the efficacy of anticancer agents.

Magnetoliposomes Based on Magnetic/Plasmonic Nanoparticles Loaded with Tricyclic Lactones for Combined Cancer Therapy.

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.

Synthesis of Novel Methyl 7-[(Hetero)arylamino]thieno[2,3-]pyrazine-6-carboxylates and Antitumor Activity Evaluation: Effects in Human Tumor Cells Growth, Cell Cycle Analysis, Apoptosis and Toxicity in Non-Tumor Cells.

Several novel methyl 7-[(hetero)arylamino]thieno[2,3-]pyrazine-6-carboxylates were synthesized by Pd-catalyzed C-N Buchwald-Hartwig cross-coupling of either methyl 7-aminothieno[3,2-]pyrazine-6-carboxylate with (hetero)arylhalides or 7-bromothieno[2,3-]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).

Synthesis of Novel Methyl 3-(hetero)arylthieno[3,2-]pyridine-2-carboxylates and Antitumor Activity Evaluation: Studies In Vitro and In Ovo Grafts of Chick Chorioallantoic Membrane (CAM) with a Triple Negative Breast Cancer Cell Line.

A series of novel functionalized methyl 3-(hetero)arylthieno[3,2-]pyridine-2-carboxylates - were synthesized by C-C Pd-catalyzed Suzuki-Miyaura cross-coupling of methyl 3-bromothieno[3,2-]pyridine-2-carboxylate with (hetero)aryl pinacol boranes, trifluoro potassium boronate salts or boronic acids. Their antitumoral potential was evaluated in two triple negative breast cancer (TNBC) cell lines-MDA-MB-231 and MDA-MB-468, by sulforhodamine B assay. Their effects on the non-tumorigenic MCF-12A cells were also evaluated.

Magnetoliposomes Containing Calcium Ferrite Nanoparticles for Applications in Breast Cancer Therapy.

Magnetoliposomes containing calcium ferrite (CaFeO) nanoparticles were developed and characterized for the first time. CaFeO nanoparticles were covered by a lipid bilayer or entrapped in liposomes forming, respectively, solid or aqueous magnetoliposomes as nanocarriers for new antitumor drugs. The magnetic nanoparticles were characterized by UV/Visible absorption, XRD, HR-TEM, and SQUID, exhibiting sizes of 5.

Novel dehydropeptide-based magnetogels containing manganese ferrite nanoparticles as antitumor drug nanocarriers.

Herein, novel dehydropeptide-based magnetogels, based on the hydrogelators Npx-l-Phe-Z-ΔAbu-OH, Npx-l-Trp-Z-ΔPhe-OH and Npx-l-Ala-Z-ΔPhe-Gly-l-Arg-Gly-l-Asp-Gly-OH and containing manganese ferrite nanoparticles (diameters around 20 nm), were prepared and characterized. TEM and FTIR measurements showed that the magnetogels maintained the fibrous structure of neat hydrogels, with fibres of ca. 20 nm average width (generally in the range 10-30 nm) and a few conformational changes relative to the neat hydrogels.

Development of Multifunctional Liposomes Containing Magnetic/Plasmonic MnFe₂O₄/Au Core/Shell Nanoparticles.

Multifunctional liposomes containing manganese ferrite/gold core/shell nanoparticles were developed. These magnetic/plasmonic nanoparticles were covered by a lipid bilayer or entrapped in liposomes, which form solid or aqueous magnetoliposomes as nanocarriers for simultaneous chemotherapy and phototherapy. The core/shell nanoparticles were characterized by UV/Visible absorption, X-Ray Diffraction (XRD), Transmission Electron Microscopy (TEM), and Superconducting Quantum Interference Device (SQUID).

Solid and aqueous magnetoliposomes as nanocarriers for a new potential drug active against breast cancer.

Iron oxide nanoparticles, with diameters around 12nm, were synthesized by coprecipitation method. The magnetic properties indicate a superparamagnetic behavior with a coercive field of 9.7Oe and a blocking temperature of 118K.

Chemical characterization, antioxidant, anti-inflammatory and cytotoxic properties of bee venom collected in Northeast Portugal.

Bee venom (BV) or apitoxin is a complex mixture of substances with reported biological activity. In the present work, five bee venom samples obtained from Apis mellifera iberiensis from the Northeast Portugal (two different apiaries) were chemically characterized and evaluated for their antioxidant, anti-inflammatory and cytotoxic properties. The LC/DAD/ESI-MS(n) analysis of the samples showed that melittin was the most abundant compound, followed by phospholipase A2 and apamin.

Bioactive Properties of Tabebuia impetiginosa-Based Phytopreparations and Phytoformulations: A Comparison between Extracts and Dietary Supplements.

Tabebuia impetiginosa (Mart. ex DC.) Standl.

Dehydrodipeptide Hydrogelators Containing Naproxen N-Capped Tryptophan: Self-Assembly, Hydrogel Characterization, and Evaluation as Potential Drug Nanocarriers.

In this work, we introduce dipeptides containing tryptophan N-capped with the nonsteroidal anti-inflammatory drug naproxen and C-terminal dehydroamino acids, dehydrophenylalanine (ΔPhe), dehydroaminobutyric acid (ΔAbu), and dehydroalanine (ΔAla) as efficacious protease resistant hydrogelators. Optimized conditions for gel formation are reported. Transmission electron microscopy experiments revealed that the hydrogels consist of networks of micro/nanosized fibers formed by peptide self-assembly.

The contribution of phenolic acids to the anti-inflammatory activity of mushrooms: Screening in phenolic extracts, individual parent molecules and synthesized glucuronated and methylated derivatives.

In the present study, the ethanolic extracts of fourteen edible mushrooms were investigated for their anti-inflammatory potential in LPS (lipopolysaccharide) activated RAW 264.7 macrophages. Furthermore the extracts were chemically characterized in terms of phenolic acids and related compounds.

Synthesis, antiangiogenesis evaluation and molecular docking studies of 1-aryl-3-[(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas: Discovery of a new substitution pattern for type II VEGFR-2 Tyr kinase inhibitors.

The synthesis and biological evaluation of novel 1-aryl-3-[2-, 3- or 4-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 3, 4 and 5 as VEGFR-2 tyrosine kinase inhibitors, are reported. The 1-aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 4a-4h, with the arylurea in the meta position to the thioether, showed the lowest IC₅₀ values in enzymatic assays (10-206 nM), the most potent compounds 4d-4h (IC₅₀ 10-28 nM) bearing hydrophobic groups (Me, F, CF₃ and Cl) in the terminal phenyl ring. A convincing rationalization was achieved for the highest potent compounds 4 as type II VEGFR-2 inhibitors, based on the simultaneous presence of: (1) the thioether linker and (2) the arylurea moiety in the meta position.

Is honey able to potentiate the antioxidant and cytotoxic properties of medicinal plants consumed as infusions for hepatoprotective effects?

Due to the enormous variety of phytochemicals present in plants, their extracts have been used for centuries in the treatment of innumerable diseases, being perceived as an invaluable source of medicines for humans. Furthermore, the combination of different plants was reported as inducing an improved effect (synergism) in comparison with the additive activity of the plants present in those mixtures. Nevertheless, information regarding the effects of plant infusions added with honey is still rather scarce.

Chemical characterisation and bioactive properties of Prunus avium L.: the widely studied fruits and the unexplored stems.

The aim of this study was to characterise sweet cherry regarding nutritional composition of the fruits, and individual phytochemicals and bioactive properties of fruits and stems. The chromatographic profiles in sugars, organic acids, fatty acids, tocopherols and phenolic compounds were established. All the preparations (extracts, infusions and decoctions) obtained using stems revealed higher antioxidant potential than the fruits extract, which is certainly related with its higher phenolic compounds (phenolic acids and flavonoids) concentration.

Bioactivity of phenolic acids: metabolites versus parent compounds: a review.

Phenolic acids are present in our diet in different foods, for example mushrooms. Due to their bioactive properties, phenolic acids are extensively studied and there is evidence of their role in disease prevention. Nevertheless, in vivo, these compounds are metabolized and circulate in the organism as glucuronated, sulphated and methylated metabolites, displaying higher or lower bioactivities.

Chemical features of Ganoderma polysaccharides with antioxidant, antitumor and antimicrobial activities.

Ganoderma genus comprises one of the most commonly studied species worldwide, Ganoderma lucidum. However, other Ganoderma species have been also reported as important sources of bioactive compounds. Polysaccharides are important contributors to the medicinal properties reported for Ganoderma species, as demonstrated by the numerous publications, including reviews, on this matter.

Antimicrobial Activity and Mechanism of Action of New N-Heteroaryl-1H-(benz)Imidazoles.

The antimicrobial activity of sixteen new N-heteroarylated 1H-(benz)imidazoles was evaluated against clinically relevant bacteria (Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa) and fungi (Candida, Aspergillus and dermatophyte) species according to the Clinical and Laboratory Standards Institute guidelines. None of the tested compounds were active against Gram negative bacteria, but only against S. aureus, that was particularly susceptible to N-thianthrenyl- and N-dibenzothienyl imidazole derivatives.

Coprinopsis atramentaria extract, its organic acids, and synthesized glucuronated and methylated derivatives as antibacterial and antifungal agents.

Despite the available data regarding antimicrobial activity of phenolic acids, studies dealing with the effects of their metabolites or derivatives are scarce. Therefore, the antimicrobial and demelanizing activities of Coprinopsis atramentaria extract, its organic acids, and methylated and glucuronated derivatives were evaluated. The antifungal activity was stronger than the antibacterial effects.

New insights into the effects of formulation type and compositional mixtures on the antioxidant and cytotoxic activities of dietary supplements based-on hepatoprotective plants.

Artichoke (A), borututu (B) and milk thistle (M) are included in several supplements to provide beneficial effects. Different formulations (infusions, pills and syrups), with different proportions of A, B and M (1 : 1 : 1, 2 : 1 : 1, 1 : 2: 1, 1 : 1 : 2) within each formulation, were assayed to optimize the desired benefits. The antioxidant activity, anti-hepatocellular carcinoma activity, hepatotoxicity and bioactive compound contents were evaluated.

Cytotoxicity of Portuguese propolis: the proximity of the in vitro doses for tumor and normal cell lines.

With a complex chemical composition rich in phenolic compounds, propolis (resinous substance collected by Apis mellifera from various tree buds) exhibits a broad spectrum of biological activities. Recently, in vitro and in vivo data suggest that propolis has anticancer properties, but is the cytoxicity of propolis specific for tumor cells? To answer this question, the cytotoxicity of phenolic extracts from Portuguese propolis of different origins was evaluated using human tumor cell lines (MCF7-breast adenocarcinoma, NCI-H460-non-small cell lung carcinoma, HCT15-colon carcinoma, HeLa-cervical carcinoma, and HepG2-hepatocellular carcinoma), and non-tumor primary cells (PLP2). The studied propolis presented high cytotoxic potential for human tumor cell lines, mostly for HCT15.