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

Abstract

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

References

Aug 1, 1979·Journal of Pharmaceutical Sciences·A P De Leenheer, H J Nelis
May 10, 1975·Journal of the American Chemical Society·D E Williamson, G W Everett
Jun 14, 1991·Science·S B Prusiner
Aug 1, 1972·Antimicrobial Agents and Chemotherapy·L A MitscherT D Sokoloski
Oct 1, 1968·Tetrahedron Letters·L A MitscherT D Sokoloski
Dec 24, 1982·Science·D C BoltonS B Prusiner
Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K M PanF E Cohen
Apr 8, 1993·Nature·G ForloniF Tagliavini
Apr 6, 1996·Lancet·R G WillP G Smith
Oct 10, 1997·Science·S B Prusiner
Mar 10, 1998·Journal of Computer-aided Molecular Design·I J BrunoM L Verdonk
Mar 31, 1998·Journal of Pharmaceutical Sciences·H F Dos SantosM C Zerner
May 20, 1998·Cell·S B PrusinerF E Cohen
Sep 2, 1998·Journal of Pharmaceutical Sciences·W B De AlmeidaM C Zerner
Jan 6, 1999·Journal of Pharmaceutical Sciences·H A DuarteA M Simas
May 31, 2001·Microbiology and Molecular Biology Reviews : MMBR·I Chopra, M Roberts

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Citations

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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