In vitro and in silico studies of polycondensed diazine systems as anti-infective agents

Infective diseases caused by protozoarian agents are still relevant today more than ever. In fact, they represent the first cause of death all over the world with seventeen millions victims every year. The development of drug resistance and the broad diffusion of these pathologies make actual the research of new molecules able to act as selective and effective anti-infective chemotherapics.[1] Recently several polycondensed diazine derivatives, by means 1,3-dipolar cycloaddition, reactions [2, 3] were synthesized. A broad selection of these compounds chosen with a wide pattern of substitutions were submitted to biological in vitro screening against Plasmodium falciparum, Leishmania Infantum, Trypanosoma brucei e Trypanosoma cruzi, and they resulted active at micromolar level. In order to identify molecular targets able to explain the mechanism of action of these compounds, we performed Induced Fit Docking/MM-GBSA modeling studies. The obtained results give interesting indications about the probable mechanism of action of the most active compounds. [1] M. Gonzaalez, H. Cerecetto, Expert Opinion on Therapeutic Patents, 21, 2011, 699-715. [2] A. Lauria, A. Guarcello, G. Dattolo, A.M. Almerico, Tetrahedron Lett., 49, 2008, 1847-1850. [3] A. Lauria, A. Guarcello, G. Macaluso, G. Dattolo, A.M. Almerico, Tetrahedron Lett., 50, 2009, 7333-7336.