Innovación de medicamentos en un nuevo milenio / Drugs innovation in a new millenium

Los medicamentos son el bien más querido por la sociedad. Son productos de los que nadie quiere prescindir cuando los necesita. La cuestión que se plantea en este siglo XXI es la de por dónde puede dirigirse la innovación en nuevos compuestos que mejoren los que se están utilizando, a la vez que se encuentran otros para enfermedades no tratadas, en estos momentos. La solución no es fácil y deben considerarse aspectos económicos del desarrollo de la ciencia y también éticos

The optimal drug discovery strategy is probably impossible to achieve, but it is relatively simple to reach a drug discovery paradigm that integrates rational drug discovery with a strong physiology and disease focus. The paradigm must not be risk aversive, because pharmaceutical R&D is by definition high-risk, but is should balance a high-risk strategy with proper risk and resource management. The paradigm should be datadriven and should favour a «try and learn» approach to produce a high turn-over of projects in the early pipeline, because only by trying can we evaluate a new approach to disease treatment

Vanadium(V) complexes with salicylaldehyde semicarbazone derivatives bearing in vitro anti-tumor activity toward kidney tumor cells (TK-10): crystal structure of [VVO2(5-bromosalicylaldehyde semicarbazone)].

As a contribution to the development of novel vanadium complexes with pharmacologically interesting moieties, new dioxovanadium(V) semicarbazone complexes with the formula cis-VO(2)L, where L=5-bromosalicylaldehyde semicarbazone and 2-hydroxynaphtalen-1-carboxaldehyde semicarbazone have been synthesized and characterized by (1)H and (13)C NMR, Raman and FTIR spectroscopies. Results were compared with those previously reported for other three analogous complexes of this series. The five complexes were tested in three different human tumor cell lines for bioactivity as potential anti-tumor agents, showing selective cytotoxicity on TK-10 cell line. Results showed that structural modifications on the semicarbazone moiety could have a significant effect on the anti-tumor activity of the vanadium complexes. In addition, the electrochemical behavior of all the complexes was studied. No apparent correlation could be demonstrated between reduction potentials of the complexes and their anti-tumor activities. The molecular structure of the novel [V(V)O(2)(5-bromosalicylaldehyde semicarbazone)] complex was solved by X-ray diffraction methods. The vanadium atom shows a distorted square pyramidal coordination sphere. The (VO(2))(+) cation is coordinated to a nearly planar (L)(-) anion acting as a tridentate ligand through both oxygen and one nitrogen atoms.

Quinoxaline N,N'-dioxide derivatives and related compounds as growth inhibitors of Trypanosoma cruzi. Structure-activity relationships.

Quinoxaline derivatives presented good inhibitor activity of growth of Trypanosoma cruzi in in vitro assays. The 50% inhibitory doses were of the same order of that of Nifurtimox. Derivative 13, a quinoxaline N,N'-dioxide derivative, and the reduced derivatives 19 and 20 were the most cytotoxic compounds against the protozoan. Structural requirements for optimal activity were studied by computational methods. From statistical analysis we could establish a multiple correlation between activity and lipophilic properties and LUMO energy.