2. Academic Validation
  3. Synthesis, semipreparative HPLC separation, biological evaluation, and 3D-QSAR of hydrazothiazole derivatives as human monoamine oxidase B inhibitors

Synthesis, semipreparative HPLC separation, biological evaluation, and 3D-QSAR of hydrazothiazole derivatives as human monoamine oxidase B inhibitors

  • Bioorg Med Chem. 2010 Jul 15;18(14):5063-70. doi: 10.1016/j.bmc.2010.05.070.
Franco Chimenti 1,  Daniela Secci,  Adriana Bolasco,  Paola Chimenti,  Arianna Granese,  Simone Carradori,  Elias Maccioni,  M Cristina Cardia,  Matilde Yáñez,  Francisco Orallo,  Stefano Alcaro,  Francesco Ortuso,  Roberto Cirilli,  Rosella Ferretti,  Simona Distinto,  Johannes Kirchmair,  Thierry Langer
Affiliations

Affiliation

  • 1 Dipartimento di Chimica e Tecnologie del Farmaco Università degli Studi di Roma La Sapienza, P.le A. Moro 5, 00185 Roma, Italy.
PMID: 20579890 DOI: 10.1016/j.bmc.2010.05.070
Abstract

The present study reports on synthesis in high yields (70-99%), HPLC enantioseparation, inhibitory activity against human monoamino oxidases, and molecular modeling including 3D-QSAR studies, of a large series of (4-aryl-thiazol-2-yl)hydrazones (1-45). Most of the synthesized compounds proved to be potent and selective inhibitors of hMAO-B isoform in the micromolar or nanomolar range, thus demonstrating that hydrazothiazole could be considered a good pharmacophore to design new hMAO-B inhibitors. Due to the presence in some derivatives of a chiral center, we also performed a semipreparative chromatographic enantioseparation of these compounds obtained by a stereoconservative pattern. The separated enantiomers were submitted to in vitro biological evaluation to point out the stereorecognition of the active site of the Enzyme towards these structures. Finally, a 3D-QSAR study was carried out using Comparative Molecular Field Analysis (CoMFA), aiming to deduce rational guidelines for the further structural modification of these lead compounds.

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