A series of seven 2-amino-4-arylthiazoles were prepared following Hantzsch’s modified method under microwave irradiation. A set of 50 derivatives was obtained and the in vitro activity against Giardia intestinalis was evaluated. The results on the biological activity revealed that, in general, the N-(5-bromo-4-aryl-thiazol-2-yl)-acetamide scaffold showed high bioactivity. In particular, compounds 6e (IC50 = 0.39 μM) and 6b (IC50 = 0.87 μM) were found to be more potent than the positive control metronidazole. Citoxicity and acute toxicity tests performed showed low toxicity and high selectivity of the most active compounds (6e SI = 139, 6b SI = 52.3). A QSAR analysis was applied to a data set of 37 obtained 2-amino-4-arylthiazoles derivatives and the best model described a strongly correlation between the anti-giardiasic activity and molecular descriptors as E2M, RDF115m, F10, MATS6v, and Hypnotic-80, with high statistical quality. This finding indicates that N-substituted aminothiazole scaffold should be investigated for the development of highly selective anti-giardial agent.
 (a) Escobedo A.A., Almirall P., Robertson L.J., Franco R.M.B., Hanevik K., Mørch K., Cimerman S. Giardiasis: the ever-present threat of a neglected disease, Infect. Disord.-Drug Targets., 2010, 10, 329-348. (b) Roxström-Lindquist, K., Palm, D., Reiner, D., Ringqvist, E., Svärd, S.G., Giardia immunity - an update, Trends Parasitol., 2006, 22, 26-31.
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