Tetracycline and its analogues as inhibitors of amyloid fibrils: searching for a geometrical pharmacophore by theoretical investigation of their conformational behavior in aqueous solution

Journal of Molecular Modeling
Ugo CosentinoM Salmona


Tetracycline (TC) and its derivatives have recently been proposed as a new class of antagonists in prion diseases as they prevent the aggregation of prion protein peptides and their acquisition of protease resistance in vitro and in vivo. Looking for relationships between conformational flexibility and biological activity, we searched for a geometrical pharmacophore by investigating, in aqueous solution, the conformational behavior of 15 TCs in both the zwitterionic and the anionic forms. For TC similar conformational flexibility was found for the two forms and two main conformational families were detected, an extended and a folded conformation characterized by different intramolecular hydrogen-bond networks. On comparing the Molecular Mechanics results with the ab initio ones and the experimental evidence, it can be seen that the conformational behavior of TC is reasonably well predicted by the MM2 force field, whereas the conformational energies provided by the Amber force field are unreliable. The conformational analysis of the other TC derivatives was then performed by the MM2 force field. As a result, their conformational behavior was similar to that observed for TC itself. Despite the hydronaphthacene moiety's conformati...Continue Reading


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May 1, 2007·Theoretical Chemistry Accounts·Giorgio MoroGiuseppe Zampella
May 4, 2006·Journal of Molecular Modeling·Olaf G OthersenTimothy Clark
Jul 17, 2008·Journal of Molecular Modeling·Ugo CosentinoMario Salmona
Jul 28, 2010·Physical Chemistry Chemical Physics : PCCP·Benedetta CarlottiFausto Elisei
Apr 4, 2017·Japanese Journal of Infectious Diseases·Sanae KurakadoTakashi Sugita
Sep 13, 2018·International Journal of Molecular Sciences·Sofia GiorgettiFrancesco Antonio Aprile
Apr 25, 2013·Journal of Medicinal Chemistry·Tatiana StoilovaMario Salmona

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