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2017
Vinhas, R, Mendes R, Fernandes {AR}, Baptista {PV}.  2017.  Nanoparticles-Emerging potential for managing leukemia and lymphoma, dec. Frontiers in Bioengineering and Biotechnology. 5: Frontiers Media Abstract

Nanotechnology has become a powerful approach to improve the way we diagnose and treat cancer. In particular, nanoparticles (NPs) possess unique features for enhanced sensitivity and selectivity for earlier detection of circulating cancer biomarkers. In vivo, NPs enhance the therapeutic efficacy of anticancer agents when compared with con-ventional chemotherapy, improving vectorization and delivery, and helping to overcome drug resistance. Nanomedicine has been mostly focused on solid cancers due to take advantage from the enhanced permeability and retention (EPR) effect experienced by tissues in the close vicinity of tumors, which enhance nanomedicine's accumulation and, consequently, improve efficacy. Nanomedicines for leukemia and lymphoma, where EPR effect is not a factor, are addressed differently from solid tumors. Nevertheless, NPs have provided innovative approaches to simple and non-invasive methodologies for diagnosis and treatment in liquid tumors. In this review, we consider the state of the art on different types of nanoconstructs for the management of liquid tumors, from preclinical studies to clinical trials. We also discuss the advantages of nanoplatforms for theranostics and the central role played by NPs in this combined strategy.

Raposo, {LR }, Roma-Rodrigues C, Jesus J, Martins {LMDRS, Pombeiro {AJL }, Baptista {PV }, Fernandes {AR }.  2017.  Targeting canine mammary tumours via gold nanoparticles functionalized with promising Co(II) and Zn(II) compounds, dec. Veterinary and Comparative Oncology. 15:1537–1542., Number 4: Wiley-Blackwell Abstract

Background: Despite continuous efforts, the treatment of canine cancer has still to deliver effective strategies. For example, traditional chemotherapy with doxorubicin and/or docetaxel does not significantly increase survival in dogs with canine mammary tumors (CMTs). Aims: Evaluate the efficiency of two metal compounds [Zn(DION)2]Cl (TS26

Vinhas, R, Cordeiro M, Pedrosa P, Fernandes {AR}, Baptista {PV}.  2017.  Current trends in molecular diagnostics of chronic myeloid leukemia, aug. Leukemia & Lymphoma. 58:1791–1804., Number 8: TAYLOR & FRANCIS LTD Abstract

Nearly 1.5 million people worldwide suffer from chronic myeloid leukemia (CML), characterized by the genetic translocation t(9;22)(q34;q11.2), involving the fusion of the Abelson oncogene (ABL1) with the breakpoint cluster region (BCR) gene. Early onset diagnosis coupled to current therapeutics allow for a treatment success rate of 90, which has focused research on the development of novel diagnostics approaches. In this review, we present a critical perspective on current strategies for CML diagnostics, comparing to gold standard methodologies and with an eye on the future trends on nanotheranostics.

Chagas, R, Lourenco AM, Monteiro S, Ferreira RB, Ferreira LM.  2017.  Is caffeic acid, as the major metabolite present in Moscatel wine protein haze hydrolysate, involved in protein haze formation?, AUG FOOD RESEARCH INTERNATIONAL. 98:103-109., Number SI: Ctr Reference Educ & Res Viticulture & Oenol; Univ Appl Sci & Arts Western Switzerland; Canadian Inst Food Sci & Technol Abstract
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Gouveia, J.P., Dias L, Seixas J, Simões S.  2017.  INSMART – Integrative Energy Planning For Cities Low Carbon Futures: Analytical Framework, 8th February. 3rd Energy for Sustainability Conference. , Funchal, Portugal
Dias, L., Simões S, Gouveia JP, Seixas J.  2017.  Integrative Energy Planning For Cities Low Carbon Futures: Modelling and Scenarios results, 8th February. 3rd Energy for Sustainability Conference. , Funchal, Portugal
Araújo, N, Fernandes C, Moniz AB, Barata J.  2017.  Additive technology safety issues: Impact on the related job design in industry, 7-8 Sep. 2017. 4º Congresso Internacional sobre Condições de Trabalho. , Porto: Rede de Investigação sobre Condições de Trabalho (RICOT) Abstract

The embedding of technology and the digitalization of processes and services within industry holds the promise for increased flexibility and productivity. Associated with the tendencies within industry 4.0 there are several enabling technologies, such has 3D printing and additive manufacturing technologies that are becoming very popular and used for industrial processes, although not without hazard. With the present paper the authors aim to explore the impacts industrial 3D printing on health and safety at work and design possible industrial intervention measures.
The technological process underneath 3D printing by itself encompasses hazardous exposure scenarios, for example: i) those that imply that thermoplastics are heated, nozzle extruded and then deposited onto a surface to build a part. Thus, by-product nanoparticles (< 1/10.000 of a millimetre) are emitted; ii) for low temperature polylactic acid (PLA) 20 billion of particles per minute can be released; iii) at higher temperatures acrylonitrile butadiene styrene (ABS) feedstock can release up to 200 billion nanoparticles.
The raw materials, can have multiple uses (e.g. raw material or support materials), origins (e.g. metallic, plastic) and forms (e.g. solid, powder). These materials encompass hazards related with: i) harmful chemicals, used mainly on support materials that are used to allow the creation of empty spaces on printed parts, such as phenyl phosphates, hazardous during use and disposal; ii) the use of metal powders, such as titanium and aluminium can spontaneously combust causing fires; iii) hot surfaces, high voltage, ultraviolet radiation, laser and moving parts are important hazards related with 3D printing machines.
Occupational health and safety measures must deal with: 1. technology that allows the contention of the hazardous agent emission without compromising the production process – for example by airtight chambers, ventilation and exhaustion chambers; 2. Compliance with ATEX directives, for metal powders use; 3. development of training and certification requirements for operating 3D industrial processes and to capacitate workers (materials, techniques, best practises); 4. Making available protective equipment’s that respond to the hazards.
There are many practical challenges related with occupational health and safety, for 3D printing technologies industrial incorporation and ownership. It’s known that hazardous materials are released during the fabrication processes, although the exposure scenarios are not well known or studied. More robust experiments and sophisticated control methods are needed to know and tackle the hazards for 3Dprinting use in industrial contexts – the size and distribution of particles (including nanoparticles), its concentration, its mass and the total volatile organic compound (COV). The study of Huang et al (2013) on societal impact develops these issues.
Since the product safety regulations depend currently on centralized manufacturing (safety testing and regular inspection in factories), 3D printing is expected to bring a dispersion of manufacturing, raising questions about safety issues. Some authors suggests that even if we move the regulation process from the products to the software of the manufacturing process in 3D-printing, concerns still remain due to the poor success of the information regulation on line as well as to the scarce ability to stop the distribution of files, particularly when combined with jurisdictional concerns.

Sulim, O, Ribeiro R, Esteves I, Antunes C, Garate A, Duarte P, Ferreira I, Mota J, Plaza M.  2017.  Design of structured adsorbents for aplications in gas adsorption processes - Conventional shaping vs 3D-Printed formulation, 5-10 March. Abstract

Microporous materials highly activated and with potential to be used as adsorbents in many applications for gas
separation/purification are usually available as powders. These solids usually have a great and reversible gas
uptake, high gas selectivity, good chemical and thermal stability, but are unsuitable to be used in gas adsorption
processes, such as Pressure Swing Adsorption (PSA) or Simulated Moving Bed (SMB).
Zeolites, carbons and more recently metal-organic frameworks (MOFs) are examples of those materials. Their
use in adsorption-based processes are dependent of their upgrading from powders (micrometer scale) to
particles (pellets, spheres or granules at millimeter scale). This would overcome large pressure drops and
consequent energy consumptions when packing adsorbent columns in those processes. Thus, shaping
adsorbents is an important step to use them in industry, although it greatly affects their capacity and selectivity
towards a specific gas separation.
In this work, we explore techniques to shape powdered adsorbents, followed by their textural and mechanical
characterizations, and the study of their adsorption properties towards the main components of post-combustion
flues gases (CO2 and N2). Materials densification is proposed by employing two approaches:
- Conventional shaping through binderless mechanical compression and binder-containing extrusion; and
- Formulation by 3D printing (or additive manufacturing) to produce packed bed morphologies that
precisely replicate computer aided design (CAD) models.
Porous separation media are important for fluid-solid contacting in many unit operations, including adsorption.
Due to practical limitations, media particles are typically packed randomly into a column in a shaped form,
allowing fluid to flow through the interstitial voids. Key to the effectiveness of packed columns are the flowrelated properties of mass transfer, fluid distribution and dispersion, and back pressure, which in turn depend
upon packing geometry. Until now, no alternative was found to overcome this limitation and have optimal
ordered packing arrangements at the micron scale. 3D-Printing (or additive manufacturing) brings a wide range
of benefits that traditional methods of manufacturing or prototyping simply cannot. With this approach, complex
ordered geometries, that are not possible by conventional extrusion, can be designed and printed for a porous
media, being the equipment resolution the only limiting step to overcome.
The effect of parameters like compression force, particle sieving, binder nature, binder/adsorbent ratio were
firstly studied using conventional shaping techniques, as a basis for the consequent development of 3D-printed
formulations. The structured samples are then characterized and adsorption equilibria studies are performed on
them to evaluate their performance as media for gas adsorption separation processes. A volumetric/manometric
adsorption unit built in-house was used for this purpose. Relevant experimental data is obtained, which allows to
conclude that 3D-printed media can be an alternative porous media for application in gas adsorption processes.

Flores, M, Seixas J.  2017.   How the European Directive cost-effectiveness model to nZEB fails widely 2050 decarbonisation goals., 29-30 Oct. XIII Congresso Ibero-Americano de Engenharia Mecânica. , Lisboa, Portugal
Seixas, J, Simões S, Fortes P, Gouveia JP.  2017.  The pivotal role of electricity to the deep decarbonization of energy system: cost-effectiveness options for Portugal, 29-30 June. 3rd International Conference on Energy and Environment. , Porto, Portugal: Faculty of Economics, University of Porto
Raposo, LR, Roma-Rodrigues C, Jesus J, Martins LMDRS, Pombeiro AJ, Baptista PV, Fernandes AR.  2017.  Targeting canine mammary tumours via gold nanoparticles functionalized with promising Co(II) and Zn(II) compounds, 2017/12/01. Veterinary and Comparative Oncology. 15(4):1537-1542.: Blackwell Publishing Ltd AbstractWebsite

Background: Despite continuous efforts, the treatment of canine cancer has still to deliver effective strategies. For example, traditional chemotherapy with doxorubicin and/or docetaxel does not significantly increase survival in dogs with canine mammary tumors (CMTs).Aims: Evaluate the efficiency of two metal compounds [Zn(DION)2]Cl (TS262, DION = 1,10-phenanthroline-5,6-dione) and [CoCl(H2O)(DION)2][BF4] (TS265) and novel nanovectorizations designed to improve the anti-cancer efficacy of these compounds in a new CMT derived cell line (FR37-CMT).
Materials and methods: FR37-CMT cells were exposed to different concentrations of TS262 and TS265 and two new nanoparticle systems and cellular viability was determined. These nanosystems are composed of polyethylene-glycol, bovine-serum-albumin and TS262 or TS265 (NanoTS262 or NanoTS265, respectively).
Results: In FR37-CMT, TS262 and TS265 displayed IC50 values well below those displayed by doxorubicin and cisplatin. The nanovectorizations further decreased the IC50 values.
Discussion: TS262 and TS265 proved to be effective against FR37-CMT cells and more effective than of doxorubicin and cisplatin. The Nanosystems efficiently delivered the cytotoxic cargo inducing a significant reduction of cell viability in FR37-CMT cell line when compared to the free compounds.
Conclusions: TS262 and TS265 are compounds with potential in the treatment of CMTs. NanoTS262 and NanoTS265 demonstrate that such simple nanovectorization via gold nanoparticles shows tremendous potential as anti-cancer formulations, which may easily be expanded to suit other cargo.

dos Santos, R, Carvalho AL, Roque CAA.  2017.  Renaissance of protein crystallization and precipitation in biopharmaceuticals purification, 2017/1//. Biotechnology Advances. 35(1):41-50. AbstractWebsite

AbstractThe current chromatographic approaches used in protein purification are not keeping pace with the increasing biopharmaceutical market demand. With the upstream improvements, the bottleneck shifted towards the downstream process. New approaches rely in Anything But Chromatography methodologies and revisiting former techniques with a bioprocess perspective. Protein crystallization and precipitation methods are already implemented in the downstream process of diverse therapeutic biological macromolecules, overcoming the current chromatographic bottlenecks. Promising work is being developed in order to implement crystallization and precipitation in the purification pipeline of high value therapeutic molecules. This review focuses in the role of these two methodologies in current industrial purification processes, and highlights their potential implementation in the purification pipeline of high value therapeutic molecules, overcoming chromatographic holdups.

Moro, AJ, Parola AJ, Pina F, Pana AM, Badea V, Pausescu I, Shova S, Cseh L.  2017.  2,2'-Spirobis chromene Derivatives Chemistry and Their Relation with the Multistate System of Anthocyanins, 2017. Journal of Organic Chemistry. 82(10):5301-5309. AbstractWebsite
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Pinto, A, Svahn N, Lima JC, Rodriguez L.  2017.  Aggregation induced emission of gold(I) complexes in water or water mixtures, 2017. Dalton Transactions. 46(34):11125-11139. AbstractWebsite
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Bule, P, Alves VD, Israeli-Ruimy V, Carvalho AL, Ferreira LMA, Smith SP, Gilbert HJ, Najmudin S, Bayer EA, Fontes CMGA.  2017.  Assembly of Ruminococcus flavefaciens cellulosome revealed by structures of two cohesin-dockerin complexes, 2017. Scientific Reports. 7:759. AbstractWebsite

Cellulosomes are sophisticated multi-enzymatic nanomachines produced by anaerobes to effectively deconstruct plant structural carbohydrates. Cellulosome assembly involves the binding of enzyme-borne dockerins (Doc) to repeated cohesin (Coh) modules located in a non-catalytic scaffoldin. Docs appended to cellulosomal enzymes generally present two similar Coh-binding interfaces supporting a dual-binding mode, which may confer increased positional adjustment of the different complex components. Ruminococcus flavefaciens’ cellulosome is assembled from a repertoire of 223 Doc-containing proteins classified into 6 groups. Recent studies revealed that Docs of groups 3 and 6 are recruited to the cellulosome via a single-binding mode mechanism with an adaptor scaffoldin. To investigate the extent to which the single-binding mode contributes to the assembly of R. flavefaciens cellulosome, the structures of two group 1 Docs bound to Cohs of primary (ScaA) and adaptor (ScaB) scaffoldins were solved. The data revealed that group 1 Docs display a conserved mechanism of Coh recognition involving a single-binding mode. Therefore, in contrast to all cellulosomes described to date, the assembly of R. flavefaciens cellulosome involves single but not dual-binding mode Docs. Thus, this work reveals a novel mechanism of cellulosome assembly and challenges the ubiquitous implication of the dual-binding mode in the acquisition of cellulosome flexibility.

Mendoza, J, Basilio N, Dangles O, Mora N, Al Bittar S, Pina F.  2017.  Binding of the five multistate species of the anthocyanin analog 7-beta-D-glucopyranosyloxy-4'-hydroxyflavylium to the beta-cyclodextrin derivative captisol, 2017. Dyes and Pigments. 143:479-487. AbstractWebsite
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Fernandes, SN, Almeida PL, Monge N, Aguirre LE, Reis D, de Oliveira CLP, Neto AMF, Pieranski P, Godinho MH.  2017.  Cellulose Nanocrystals: Mind the Microgap in Iridescent Cellulose Nanocrystal Films (Adv. Mater. 2/2017), 2017. Advanced MaterialsAdvanced Materials. 29(2): John Wiley & Sons, Ltd AbstractWebsite

Cellulose nanocrystals are isolated from plant cellulose structures, e.g., cotton. In article 1603560, M. H. Godinho and co-workers describe a tunable photonic material produced from these cellulose nanocrystals iridescent films, which reflects both right- and left-handed circularly polarized light, taking advantage of the gaps existing along the cellulose nanocrystals films that are filled with a nematic liquid crystal.

Huang, RJ, Avo J, Northey T, Chaning-Pearce E, dos Santos PL, Ward JS, Data P, Etherington MK, Fox MA, Penfold TJ, Berberan-Santos MN, Lima JC, Bryce MR, Dias FB.  2017.  The contributions of molecular vibrations and higher triplet levels to the intersystem crossing mechanism in metal-free organic emitters, 2017. Journal of Materials Chemistry C. 5(25):6269-6280. AbstractWebsite
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Czerwinska, K, Machura B, Kula S, Krompiec S, Erfurt K, Roma-Rodrigues C, Fernandes AR, Shul'pina LS, Ikonnikov NS, Shul'pin GB.  2017.  Copper(ii) complexes of functionalized 2,2[prime or minute]:6[prime or minute],2[prime or minute][prime or minute]-terpyridines and 2,6-di(thiazol-2-yl)pyridine: structure, spectroscopy, cytotoxicity and catalytic activity, 2017. Dalton Transactions. 46(29):9591-9604.: The Royal Society of Chemistry AbstractWebsite

Six new copper(ii) complexes with 2,2[prime or minute]:6[prime or minute],2[prime or minute][prime or minute]-terpyridine (4[prime or minute]-Rn-terpy) [1 (R1 = furan-2-yl), 2 (R2 = thiophen-2-yl), and 3 (R3 = 1-methyl-1H-pyrrol-2-yl)] and 2,6-di(thiazol-2-yl)pyridine derivatives (Rn-dtpy) [4 (R1), 5 (R2), and 6 (R3)] have been synthesized by a reaction between copper(ii) chloride and the corresponding ligand. The complexes have been characterized by UV-vis and IR spectroscopy, and their structures have been determined by X-ray analysis. The antiproliferative potential of copper(ii) complexes of 2,2[prime or minute]:6[prime or minute],2[prime or minute][prime or minute]-terpyridine and 2,6-di(thiazol-2-yl)pyridine derivatives towards human colorectal (HCT116) and ovarian (A2780) carcinoma as well as towards lung (A549) and breast adenocarcinoma (MCF7) cell lines was examined. Complex 1 and complex 6 were found to have the highest antiproliferative effect on A2780 ovarian carcinoma cells, particularly when compared with complex 2, 3 with no antiproliferative effect. The order of cytotoxicity in this cell line is 6 > 1 > 5 > 4 > 2 [approximate] 3. Complex 2 seems to be much more specific towards colorectal carcinoma HCT116 and lung adenocarcinoma A549 cells. The viability loss induced by the complexes agrees with Hoechst 33258 staining and typical morphological apoptotic characteristics like chromatin condensation and nuclear fragmentation. The specificity towards different types of cell lines and the low cytotoxic activity towards healthy cells are of particular interest and are a positive feature for further developments. Complexes 1-6 were also tested in the oxidation of alkanes and alcohols with hydrogen peroxide and tert-butyl-hydroperoxide (TBHP). The most active catalyst 4 gave, after 120 min, 0.105 M of cyclohexanol + cyclohexanone after reduction with PPh3. This concentration corresponds to a yield of 23% and TON = 210. Oxidation of cis-1,2-dimethylcyclohexane with m-CPBA catalyzed by 4 in the presence of HNO3 gave a product of a stereoselective reaction (trans/cis = 0.47). Oxidation of secondary alcohols afforded the target ketones in yields up to 98% and TON = 630.

Cruz, H, Jordao N, Branco LC.  2017.  Deep eutectic solvents (DESs) as low-cost and green electrolytes for electrochromic devices, 2017. Green Chemistry. 19(7):1653-1658. AbstractWebsite
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Santoro, S, Sebastian V, Moro AJ, Portugal CAM, Lima JC, Coelhoso IM, Crespo JG, Mallada R.  2017.  Development of fluorescent thermoresponsive nanoparticles for temperature monitoring on membrane surfaces, 2017. Journal of Colloid and Interface Science. 486:144-152. AbstractWebsite
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Tavares, M, Cabral RP, Costa C, Martins P, Fernandes AR, Casimiro T, Aguiar-Ricardo A.  2017.  Development of PLGA dry powder microparticles by supercritical CO2-assisted spray-drying for potential vaccine delivery to the lungs, 2017. 128:235-243. AbstractWebsite

In this work, biocompatible and biodegradable poly(d-l-lactide-co-glycolide) (PLGA) composite microparticles with potential use as carrier for vaccines and other drugs to the lungs were developed using supercritical CO2-assisted spray-drying (SASD). Bovine serum albumin (BSA) was chosen as model vaccine, and l-leucine as a dispersibility enhancer, and their effects on the particle characteristics were evaluated. The dry powder formulations (DPFs) were characterized in terms of their morphology and aerodynamic performance using an in vitro aerosolization study – Andersen cascade impactor (ACI) − to obtain data such as the fine particle fraction (FPF) with percentages up to 43.4%, and the mass median aerodynamic diameter (MMAD) values between the 1.7 and 3.5μm. Additionally, pharmacokinetic and cytotoxicity studies were performed confirming that the produced particles have all the necessary requirements for potential pulmonary delivery.

Lenis-Rojas, OA, Roma-Rodrigues C, Fernandes AR, Marques F, Pérez-Fernández D, Guerra-Varela J, Sánchez L, Vázquez-García D, López-Torres M, Fernández A, Fernández JJ.  2017.  Dinuclear RuII(bipy)2 Derivatives: Structural, Biological, and in Vivo Zebrafish Toxicity Evaluation, 2017. Inorganic ChemistryInorganic Chemistry. 56(12):7127-7144.: American Chemical Society AbstractWebsite

Ruthenium-based drugs exhibit interesting properties as potential anticancer pharmaceuticals. We herein present the synthesis and characterization of a new family of ruthenium complexes with formulas [{Ru(bipy)2}2(μ-L)][CF3SO3]4 (L = bptz, 1a) and [{Ru(bipy)2}2(μ-L)][CF3SO3]2 (L = arphos, 2a; dppb, 3a; dppf, 4a), which were synthesized from the Ru(II) precursor compound cis-Ru(bipy)2Cl2. The complexes were characterized by elemental analysis, mass spectrometry, 1H and 31P{1H} NMR, IR spectroscopy, and conductivity measurements. The molecular structures for three Ru(II) compounds were determined by single-crystal X-ray diffraction. The newly developed compounds interact with CT-DNA by intercalation, in particular, 2a, 3a, and 4a, which also seemed to induce some extent of DNA degradation. This effect seemed to be related with the formation of reactive oxygen species. The cytotoxic activity was evaluated against A2780, MCF7, and MDAMB231 human tumor cells. Compounds 2a and 4a were the most cytotoxic with activity compared to cisplatin (∼2 μM, 72 h) in the A2780 cisplatin sensitive cells. All the compounds induced A2780 cell death by apoptosis, however, to a lesser extent for compounds 4a and 2a. For these compounds, the mechanism of cell death in addition to apoptosis seemed to involve autophagy. In vivo toxicity was evaluated using the zebrafish embryo model. LC50 estimates varied from 5.397 (3a) to 39.404 (1a) mg/L. Considering the in vivo toxicity in zebrafish embryos and the in vitro cytotoxicity in cancer cells, compound 1a seems to be the safest having no effect on dechirionation and presenting a good antiproliferative activity against ovarian carcinoma cells.Ruthenium-based drugs exhibit interesting properties as potential anticancer pharmaceuticals. We herein present the synthesis and characterization of a new family of ruthenium complexes with formulas [{Ru(bipy)2}2(μ-L)][CF3SO3]4 (L = bptz, 1a) and [{Ru(bipy)2}2(μ-L)][CF3SO3]2 (L = arphos, 2a; dppb, 3a; dppf, 4a), which were synthesized from the Ru(II) precursor compound cis-Ru(bipy)2Cl2. The complexes were characterized by elemental analysis, mass spectrometry, 1H and 31P{1H} NMR, IR spectroscopy, and conductivity measurements. The molecular structures for three Ru(II) compounds were determined by single-crystal X-ray diffraction. The newly developed compounds interact with CT-DNA by intercalation, in particular, 2a, 3a, and 4a, which also seemed to induce some extent of DNA degradation. This effect seemed to be related with the formation of reactive oxygen species. The cytotoxic activity was evaluated against A2780, MCF7, and MDAMB231 human tumor cells. Compounds 2a and 4a were the most cytotoxic with activity compared to cisplatin (∼2 μM, 72 h) in the A2780 cisplatin sensitive cells. All the compounds induced A2780 cell death by apoptosis, however, to a lesser extent for compounds 4a and 2a. For these compounds, the mechanism of cell death in addition to apoptosis seemed to involve autophagy. In vivo toxicity was evaluated using the zebrafish embryo model. LC50 estimates varied from 5.397 (3a) to 39.404 (1a) mg/L. Considering the in vivo toxicity in zebrafish embryos and the in vitro cytotoxicity in cancer cells, compound 1a seems to be the safest having no effect on dechirionation and presenting a good antiproliferative activity against ovarian carcinoma cells.

Gago, S, Basilio N, Quintas A, Pina F.  2017.  Effect of beta-Cyclodextrin on the Multistate Species Distribution of 3-Methoxy-4',7-dihydroxyflavylium. Discrimination of the Two Hemiketal Enantiomers, 2017. Journal of Agricultural and Food Chemistry. 65(31):6346-6358. AbstractWebsite
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