Synthesis, in vitro, and in vivo biological evaluation and molecular docking simulations of chiral alcohol and ether derivatives of the 1,5-diarylpyrrole scaffold as novel anti-inflammatory and analgesic agents

  • Bioorg Med Chem. 2008 Sep 1;16(17):8072-81. doi: 10.1016/j.bmc.2008.07.058.
Mariangela Biava  1 ,  Giulio C Porretta ,  Giovanna Poce ,  Sibilla Supino ,  Fabrizio Manetti ,  Stefano Forli ,  Maurizio Botta ,  Lidia Sautebin ,  Antonietta Rossi ,  Carlo Pergola ,  Carla Ghelardini ,  Monica Norcini ,  Francesco Makovec ,  Antonio Giordani ,  Paola Anzellotti ,  Roberto Cirilli ,  Rosella Ferretti ,  Bruno Gallinella ,  Francesco La Torre ,  Maurizio Anzini ,  Paola Patrignani
Affiliations
  • 1. Dipartimento di Studi di Chimica e Tecnologie del Farmaco, Università La Sapienza, Piazzale Aldo Moro, 5, I-00185 Roma, Italy.
PMID: 18752957 DOI: 10.1016/j.bmc.2008.07.058
Abstract

Following our previous research on anti-inflammatory drugs (NSAIDs), we report here the synthesis of chiral 1,5-diarylpyrroles derivatives that were characterized for their in vitro inhibitory effects toward cyclooxygenase (COX) isozymes. Analysis of enzymatic affinity and COX-2 selectivity led us to the selection of one compound (+/-)-10b that was further tested in vitro in the human whole blood (HWB) and in vivo for its anti-inflammatory activity in mice. The affinity data have been rationalized through docking simulations.