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

Infective diseases caused by protozoarian agents are still relevant todaymore than ever. In fact, they represent the first cause of death all over the worldwith seventeen millions victims every year. The development of drug resistanceand the broad diffusion of these pathologies make actual the research of newmolecules able to act as selective and effective anti-infective chemotherapics.[1]Recently several polycondenseddiazine derivatives, by means 1,3-dipolarcycloaddition, reactions [2, 3] weresynthesized.A broad selection of thesecompounds chosen with a wide pattern ofsubstitutions were submitted to biologicalin vitro screening against Plasmodiumfalciparum, Leishmania Infantum,Trypanosoma brucei e Trypanosomacruzi, and they resulted active atmicromolar level. In order to identifymolecular targets able to explain themechanism of action of these compounds,we performed Induced Fit Docking/MM-GBSA modeling studies. The obtainedresults give interesting indications about the probable mechanism of action of themost 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.