The restoration of acetylcholine levels in the brain by inhibition of cholinesterases is currently the most successful therapeutic strategy to treat neurodegenerative disorders. In this context, tacrine has been largely investigated as a starting scaffold for the development of promising new anticholinesterases compounds for the treatment of neurodegenerative illnesses, including Alzheimer’s disease. Here we present a series of compounds containing the tacrine nucleus connected with squaric moiety by a diaminoalkylene chain. The compounds were obtained through a simple and short synthetic route and showed high inhibitory activity against acetylcholinesterase (AChE) within nanomolar IC50 (half maximal inhibitory concentration). The molecular modelling study showed that these compounds act as dual-binding inhibitors of AChE, interacting with both catalytic active site (CAS) and peripheral anionic site (PAS) of the enzyme’s binding cavity. The investigated compounds also demonstrated outstanding selectivity for AChE than in butyrylcholinesterase (BuChE). These results evince these compounds as promising agents for the treatment of neurodegenerative disorders and a fuller synthetic scope jointly with complementary biological evaluations are currently under investigation in our laboratory.

The profile analysis of CNPq Research Productivity Fellows (PQ) in the four subfields of chemistry and in their respective specialties highlighted particularities with regard to the indicators related to the judging criteria established by the Chemistry Advisory Committee. The curricula of all 727 PQ fellows with active grants in 15/03/2013 were analyzed spanning the past10 years (2003-2013). Out of all PQ-1 fellows, researchers in the subfield of Organic Chemistry had the highest median number of articles published per year. The subfield of Analytical Chemistry qualifies a higher number of postgraduate level students in comparison to other Chemistry subfields. Furthermore, this subfield had the highest average Hirsch index among PQ-1A and PQ-1B fellows. On the other hand, Inorganic Chemistry had the highest average number of patent applications per researcher, while Physical Chemistry had the specialties with the highest citation rates per paper and the highest average impact factors per journal. In all subfields, women made up a low proportion, especially at the highest levels of PQ fellowships. Although quantitative differences in scientific output were observed among the subfields, qualitative evaluation of science output was not carried out.

No presente estudo, os efeitos do chumbo (Pb) sobre o crescimento, a concentração de pigmentos fotossintéticos, a peroxidação lipídica, a percentagem de extravazamento de eletrólitos (ELP), a oxidação protéica, a atividade das enzimas aminolevulinato desidratase (ALA-D; E.C. 4.2.1.24), peroxidase do ascorbato (APX; E.C. 1.11.1.11), catalase (CAT; E.C. 1.11.1.6) e dismutase do superóxido (SOD; E.C. 1.15.1.1) e as concentrações de ácido ascórbico (AsA), de grupos tióis não-protéicos (NPSH) e de proteínas solúveis totais foram investigados em plântulas de pepino (Cucumis sativus L.). As plântulas foram cultivadas in vitro em um substrato solidificado com ágar contendo três concentrações de Pb na forma de (C2H3O2)Pb.3H2O (0, 100, 400 e 1000 µmol L-1), durante 10 dias. O aumento da concentração de Pb no substrato ocasionou um aumento da concentração de Pb tanto nas raízes quanto na parte aérea. O Pb foi acumulado em maior quantidade nas raízes. O comprimento radicular e a matéria fresca total foram diminuídos nas duas maiores concentrações de Pb. O pepino não apresentou redução no comprimento da parte aérea e na matéria seca total nos tratamento de Pb. A maior concentração de Pb diminuiu o conteúdo de água e a atividade da ALA-D bem como aumentou as concentrações de aldeído malônico, de grupos carbonil e de proteínas solúveis totais. A concentração de carotenóides aumentou em 100 e 400 µmol Pb L-1, enquanto a concentração de clorofila e a ELP não foram afetadas pelo estresse com Pb. A atividade da APX foi inibida, enquanto as atividades da CAT e SOD foram aumentadas em todas as concentrações de Pb. A concentração de AsA aumentou sob 400 e 1000 µmol Pb L-1, enquanto a de NPSH aumentou somente na maior concentração de Pb. Portanto, a exposição a altas concentrações de Pb causou estresse oxidativo e o sistema antioxidante das plântulas de pepino não foi capaz de reverter esta situação, contribuindo para a redução no crescimento.

In this study, the effects of lead (Pb) on growth, photosynthetic pigments concentration, lipid peroxidation, electrolyte leakage percentage (ELP), protein oxidation, aminolevulinate dehydratase (ALA-D; E.C. 4.2.1.24), ascorbate peroxidase (APX; E.C. 1.11.1.11), catalase (CAT; E.C. 1.11.1.6) and superoxide dismutase (SOD; E.C. 1.15.1.1) activities, and ascorbic acid (AsA), non-protein thiol groups (NPSH) and total soluble protein concentrations in cucumber seedlings (Cucumis sativus L.) were investigated. Seedlings were grown in vitro in an agar-solidified substrate containing three Pb levels as (C2H3O2)Pb.3H2O (0, 100, 400, and 1000 µmol L-1) for 10 d. Increasing Pb concentrations in substrate enhanced Pb concentration in both roots and shoot. Pb accumulated at a higher amount in roots. Root length and total fresh weight were decreased at the two highest Pb concentrations. Cucumber showed no reduction in shoot length and total dry weight at any Pb level. The highest Pb concentration decreased water content and ALA-D activity as well as increased malondialdehyde, carbonyls and total soluble protein concentrations. Carotenoids concentration enhanced at 100 and 400 µmol Pb L-1, while chlorophyll concentration and ELP were not affected by Pb stress. Activity of APX was inhibited while the activities of CAT and SOD were increased at all Pb concentrations. AsA was enhanced at 400 and 1000 µmol Pb L-1 whereas NPSH were increased only at the highest Pb concentration. Therefore, high Pb-exposure caused oxidative stress, and the antioxidant system of the cucumber seedlings was not sufficient to revert it, contributing for growth reduction.