En el Vintè aniversari de la Conferència Fèlix Serratosa

En commemoració del vintè aniversari de la celebració de la Conferència Fèlix Serratosa, es fa una ressenya dels orígens i l'evolució d'aquesta Conferència, amb menció expressa dels conferenciants que hi han participat, alguns dels quals han estat guardonats amb el Premi Nobel de Química. De manera complementària, l'article conté diferents valoracions sobre la personalitat del professor Serratosa, així com de l'impacte de la seva trajectòria com a químic sintètic en els vessants d'investigador i de mestre.On the occasion of the 20th anniversary of the Felix Serratosa Conference, a review of the origin, course and lecturers of this Conference is presented. Some of these prestigious lecturers have been awarded the Nobel Prize. Complementarily, this text contains different personal views of the professional and personal traits of professor Serratosa

Els Químics i el descobriment de fàrmacs: un repte i una necessitat

En aquest article es fa un breu relat històric del paper del químic en el descobriment de fàrmacs, per endinsar-se després en les estratègies modernes que fan servir els científics d'avui per dissenyar i produir nous medicaments que ajudin a combatre les malalties que més preocupen la societat. Finalment, es dóna una panoràmica de la possible evolució del món del descobriment de fàrmacs, de la implicació del químic en aquest món i de la contribució de grups d'investigació del nostre Institut en aquest camp.In this contribution, after a brief historical account on the role of chemists on drug discovery, a deeper insight into the modern strategies that scientists employ for the design and production of new drugs that could help to fight against the diseases that concern our society is discussed. Thereafter, an overview on the potential evolution directions of drug discovery linked to the valuable implications of chemists to assist in this evolution is given. Finally, a brief summary of the work that research groups from our Institute carry out in the Biomedicine area is also outlined

En el cinquantè aniversari del Centre d'Investigació i Desenvolupament del CSIC a Barcelona [1]

En commemoració del cinquantè aniversari de la inauguració del Centre d'Investigació i Desenvolupament (CID), el centre d'investigació química més emblemàtic del CSIC a Catalunya, es fa una ressenya dels orígens i evolució d'aquest Centre al llarg d'aquests cinquanta anys. De manera complementària, l'article conté valoracions sobre diferents canvis d'orientació i vicissituds viscudes pel CID en la seva trajectòria fins esdevenir el centre de química de l'actualitat.CID (Centre d'Investigació i Desenvolupament), CSIC, química

Vestibulotoxic properties of potential metabolites of allylnitrile

This study addressed the hypothesis that epoxidation of the double bond in allylnitrile mediates its vestibular toxicity, directly or after subsequent metabolism by epoxide hydrolases. The potential metabolites 3,4-epoxybutyronitrile and 3,4-dihydroxybutyronitrile were synthesized and characterized. In aqueous solutions containing sodium or potassium ions, 3,4-epoxybutyronitrile rearranged to 4-hydroxybut-2-enenitrile, and this compound was also isolated for study. Male adult Long-Evans rats were exposed to allylnitrile or 3,4-epoxybutyronitrile by bilateral transtympanic injection, and vestibular toxicity was assessed using a behavioral test battery and scanning electron microscopy (SEM) observation of the sensory epithelia. Overt vestibular toxicity was caused by 3,4-epoxybutyronitrile at 0.125 mmol/ear and by allylnitrile in some animals at 0.25 mmol/ear. Additional rats were exposed by unilateral transtympanic injection. In these studies, behavioral evidences and SEM observations demonstrated unilateral vestibular toxicity after 0.125 mmol of 3,4-epoxybutyronitrile and bilateral vestibular toxicity after 0.50 mmol of allylnitrile. However, 0.25 mmol of allylnitrile did not cause vestibular toxicity. Unilateral administration of 0.50 mmol of 3,4-dihydroxybutyronitrile or 4-hydroxybut-2-enenitrile caused no vestibular toxicity. The four compounds were also evaluated in the mouse utricle explant culture model. In 8-h exposure experiments, hair cells completely disappeared after 3,4-epoxybutyronitrile at concentrations of 325 or 450μM but not at concentrations of 150μM or lower. In contrast, no difference from controls was recorded in utricles exposed to 450μM or 1.5mM of allylnitrile, 3,4-dihydroxybutyronitrile, or 4-hydroxybut-2-enenitrile. Taken together, the present data support the hypothesis that 3,4-epoxybutyronitrile is the active metabolite of allylnitrile for vestibular toxicity

Synthesis, in vitro profiling, and in vivo efficacy studies of a new family of multitarget anti-Alzheimer compounds

Simultaneous modulation of several targets or pathological events with a key pathogenic role is a promising strategy to tackle thus far difficult-to-cure or incurable multifactorial diseases, such as Alzheimer's disease (AD). In this scenario, multitarget compounds, i.e., single molecules that hit several targets, are superior to other multitarget strategies that are based on the use of more than one drug (drug cocktails, fixed-dose combinations), in terms of simpler drug development and better patient compliance, efficiency, and safety. In the frame of our research line devoted to the development of novel anti-AD drug candidates, we have recently prepared a new class of multitarget compounds, which were designed by combining pharmacophoric moieties of a known antioxidant agent (7-methoxy-2,2- dimethylchroman-6-ol (CR-6)) and an acetylcholinesterase (AChE) inhibitor (6-chlorotacrine), to primarily address two important pathological events of AD, namely oxidative stress and cholinergic deficit. Here, we present the synthesis of three short series of CR-6-chlorotacrine hybrids, featuring different linker functionalities (amide, inverse amide, or amine) and lengths, and their in vitro biological activities against AChE, butyrylcholinesterase, BACE-1, and β-amyloid and tau protein aggregation, their antioxidant activity, and BBB permeability. We will also show the results of the in vivo efficacy studies of two selected compounds in double transgenic APP/PS1 mice, a wellestablished mouse model of AD (behavioral studies, effects on amyloid pathology and oxidative stress)

On the 50th anniversary of the CSIC Centre for Research and Development in Barcelona

En commemoració del cinquantè aniversari de la inauguració del Centre d’Investigació i Desenvolupament (CID), el centre d’investigació química més emblemàtic del CSIC a Catalunya, es fa una ressenya dels orígens i evolució d’aquest Centre al llarg d’aquests cinquanta anys. De manera complementària, l’article conté valoracions sobre diferents canvis d’orientació i vicissituds viscudes pel CID en la seva trajectòria fins esdevenir el centre de química de l’actualitat.Paraules clau: CID (Centre d’Investigació i Desenvolupament), CSIC, química.This is a review of the CID (Centre for Research and Development), the most emblematic CSIC (Spanish National Research Council) chemical research centre in Catalonia, on the occasion of its 50th anniversary. In connection with this event, this paper presents a personal view of the various changes in the CID’s orientation and of the vicissitudes in the course of its development, leading up to its present status as a leading chemical research centre.Keywords: CID (Centre for Research and Development), CSIC (Spanish National Research Council), chemistry