Tetraspanins: useful multifunction proteins for the possible design and development of small-molecule therapeutic tools.

Tetraspanins constitute a well-conserved superfamily of four-span small membrane proteins (TM4SF), with >30 members in humans, with important roles in numerous mechanisms of cell biology. Moreover, tetraspanins associate with either specific partner proteins or another tetraspanin, generating a network of interactions involved in cell and membrane compartmentalization and having a role in cellular development, proliferation, activation, motility, and membrane fusions. Therefore, tetraspanins are considered regulators of cellular signaling and are often depicted as 'molecular facilitators'. In view of these many physiological functions, it is likely that these molecules are important actors in pathological processes. In this review, we present the main characteristics of this superfamily, providing a more detailed description of some significant representatives and discuss their relevance as potential targets for the design and development of small-molecule therapeutics in different pathologies.

Haspin: a promising target for the design of inhibitors as potent anticancer drugs.

Protein kinases constitute a large group of enzymes in eukaryotes and have an important role in many cellular processes. Several of these proteins are active kinases, such as haploid germ cell-specific nuclear protein kinase (Haspin), an atypical eukaryotic protein kinase that lacks sequence similarity with other eukaryotic protein kinases. Haspin is a serine/threonine kinase that associates with chromosome and phosphorylates threonine 3 of histone 3 during mitosis. Haspin overexpression or deletion results in defective mitosis. It has been shown that Haspin inhibitors have potent anti-tumoral effects. Given that the only Haspin substrate is threonine 3 of histone 3, inhibition of Haspin might have fewer adverse effects compared with other anticancer agents. Here, we highlight the chemical structures and actions of currently known Haspin inhibitors.

Synthesis and evaluation of disubstituted N1- and N3-imidazolidin-2-ones acting as potential immunosuppressive agents.

New N1-mono and N1, N2-disubstituted imidazolidin-2-one with a significant immunosuppressive activity have been discovered. Among the 17 synthesized and tested compounds, five of them showed maximal inhibition of proliferation of concanavallin A (Con A)- stimulated splenocytes at 90 microM, identical to that obtained with cyclosporin A (CsA) at 5 microM, an optimal concentration.

Synthesis and antileishmanial activity of new imidazolidin-2-one derivatives.

N(3)-acyl, arylsulfonyl and benzyl derivatives of N(1)-(4,6-dimethylpyridin-2-yl), (5-methylthiazol-2-yl) or (3-methylisoxazol-5-yl)imidazolidin-2-ones were synthesized and evaluated as potential antileishmanial agents. Determination of their cytotoxic effect was carried out using MRC5 cells. Two compounds, 1-(4,6-dimethylpyridin-2-yl)-3-(napht-2-ylsulfonyl)imidazolidin-2-one, 18, and 1-(3-methylisoxazol-5-yl)-3-(4-bromobenzyl)imidazo-lidin-2-one, 25, exerted significant antileishmanial activity in promastigotes of Leishmania (L) mexicana and Leishmania infantum, with IC(50) in the range of 8-16 micro mol L(-1). Antiparasitical activity of the less toxic compound, 25, was confirmed against intracellular amastigote of L. mexicana, the clinical relevant stage; its low IC(50) value (2.4 micro mol L(-1)) and its favourable toxicity/activity index (11) constitute encouraging results for ongoing pharmacomodulation in the corresponding subseries.