Anthracyclines are ranked among the most effective chemotherapeutics against cancer. They are glycoside drugs comprising the amino sugar daunosamine linked to a hydroxy anthraquinone aglycone, and act by DNA intercalation, oxidative stress generation and topoisomerase II poisoning. Regardless of their therapeutic value, multidrug resistance and severe cardiotoxicity are important limitations of anthracycline treatment that have prompted the discovery of novel analogues. This review covers the most clinically relevant anthracyclines and their development over decades, since the first discovered natural prototypes to recent semisynthetic and synthetic derivatives. These include registered drugs, drug candidates undergoing clinical trials, and compounds under pre‐clinical investigation. The impact of the structural modifications on antitumour activity, toxicity and resistance profile is addressed.

A very simple and rapid method for the determination of total mercury in fish samples using the Direct Mercury Analyser DMA-80 was developed. In this system, a previously weighted portion of fresh fish is combusted and the released mercury is selectively trapped in a gold amalgamator. Upon heating, mercury is desorbed from the amalgamator, an atomic absorption measurement is performed and the mercury concentration is calculated. Some experimental parameters have been studied and optimised. In this study the sample mass was about 100.0 mg. The relative standard deviation was lower than 8.0% for all measurements of solid samples. Two calibration curves against aqueous standard solutions were prepared through the low linear range from 2.5 to 20.0 ng of Hg, and the high linear range from 25.0 to 200.0 ng of Hg, for which a correlation coefficient better than 0.997 was achieved, as well as a normal distribution of the residuals. Mercury reference solutions were prepared in 5.0% v/v nitric acid medium. Lyophilised fish tissues were also analysed; however, the additional procedure had no advantage over the direct analysis of the fresh fish, and additionally increased the total analytical process time. A fish tissue reference material, IAEA-407, was analysed and the mercury concentration was in agreement with the certified value, according to the t-test at a 95% confidence level. The limit of quantification (LOQ), based on a mercury-free sample, was 3.0 µg kg(-1). This LOQ is in accordance with performance criteria required by the Commission Regulation No. 333/2007. Simplicity and high efficiency, without the need for any sample preparation procedure, are some of the qualities of the proposed method.

Chagas' disease is still a worldwide threat, with estimated from 6 to 7 million infected people, mainly in Latin America. Despite all efforts, especially from international consortia (DNDi, NMTrypI), to develop an innovative therapeutic strategy against this disease, no candidate has achieved full requirements for clinical use yet. In this review, we point out the general molecular and cellular mechanisms involved in T. cruzi cell invasion and elucidate the roles of specific parasite and host targets in the progress of Chagas' disease. Among these molecular targets are Gp85/transsialidase, mucins, cruzipain and oligopeptidase B, found in parasite cell surface, and Galectin-3 and Toll-like receptors present in host cells. Thus, the deep understanding of their interplay and involvement on T. cruzi host cell adhesion, invasion and evasion from host immune may expand the chances for discovering new therapeutic agents against this neglected disease. Additionally, these targets may represent a remarkable strategy to block parasite invasion in the early stages of infection.

This work addresses the synthesis and biological evaluation of glycosyl diketopiperazines (DKPs) cyclo[Asp-(αGalNAc)Ser] 3 and cyclo[Asp-(αGalNAc)Thr] 4 for the development of novel anti-trypanosomal agents and Trypanosoma cruzi trans-sialidase (TcTS) inhibitors. The target compounds were synthetized by coupling reactions between glycosyl amino acids αGalNAc-Ser 7 or αGalNAc-Thr 8 and the amino acid (O-tBu)-Asp 17, followed by one-pot deprotection-cyclisation reaction in the presence of 20% piperidine in DMF. The protected glycosyl amino acid intermediates 7 and 8 were, in turn, obtained by α-selective, HgBr2-catalysed glycosylation reactions of Fmoc-Ser/Thr benzyl esters 12/14 with αGalN3Cl 11, being, subsequently, fully deprotected for comparative biological assays. The DKPs 3 and 4 showed relevant anti-trypanosomal effects (IC50 282-124 μM), whereas glycosyl amino acids 1 and 2 showed better TcTS inhibition (57-79%) than the corresponding DKPs (13-25%).

We demonstrate that tuning the reactivity of Cu by the choice of oxidation state and counterion leads to the activation of both "armed" and "disarmed" type glycals towards direct glycosylation leading to the α-stereoselective synthesis of deoxyglycosides in good to excellent yields. Mechanistic studies show that Cu I is essential for effective catalysis and stereocontrol and that the reaction proceeds through dual activation of both the enol ether as well as the OH nucleophile. Carbohydrates play significant roles in a wide range of biological events 1 and efficient catalytic and asymmetric methods to access this class of chiral molecules are needed to further our understanding of their various roles and functions in health and disease. 2, 3 First row transition metals have recently attracted attention as alternatives to precious metals in catalysis. 4 Among those, copper is a cost-effective, earth-abundant and sustainable metal and Cu-complexes can display unique and versatile reactivity and good functional group tolerance. 4 The chemistry exhibited by Cu can be very diverse depending on its oxidation state, as this metal can efficiently catalyse reactions involving one or twoelectron mechanisms. 4-7 In the context of O-linked glycosylation reactions, a few examples of Cu(II) as a mild oxophilic Lewis acid catalyst for the activation of oxygen-containing leaving groups have been reported. 8-11 More recently, the use of Cu II (OTf)2 as an in situ oxidant in the photoinduced-activation of thioglycosides was also exemplified. 12 However, despite copper catalysts being relatively cheap and widely available, we were surprised by the overall under exploration of this metal in glycosylation chemistry 13-17. Our group is interested in the development of sustainable and catalytic methods for the synthesis of oligosaccharides. 18-21 2deoxy-hexoses are prominent components of natural products which due to the lack of substituents at C-2 to direct the nucleophile approach present significant synthetic challenges and their improved and stereoselective protocols for their assembly has been of great intetest. 5, 18, 22-37 Previous work from our group and others has shown that activation of glycals to yield glycosides can be achieved using transition metals such as Pd(II) 38, 39 , Au(I) 40 or Re(V) 41 catalysts, however activation of sensitive enol ethers bearing electronwithdrawing groups at the C-3 position of the glycal was not possible under those conditions (Scheme 1) and in general harsher conditions used to activate such glycals often lead to donor hydrolysis and/or Ferrier type products. 26 Scheme 1: Cu I-catalysed direct synthesis of deoxyglycosides from glycals