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.
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.
Biava
Mariangela
M
Dipartimento di Studi di Chimica e Tecnologie del Farmaco, Università La Sapienza, Piazzale Aldo Moro, 5, I-00185 Roma, Italy.
Porretta
Giulio C
GC
Poce
Giovanna
G
Supino
Sibilla
S
Manetti
Fabrizio
F
Forli
Stefano
S
Botta
Maurizio
M
Sautebin
Lidia
L
Rossi
Antonietta
A
Pergola
Carlo
C
Ghelardini
Carla
C
Norcini
Monica
M
Makovec
Francesco
F
Giordani
Antonio
A
Anzellotti
Paola
P
Cirilli
Roberto
R
Ferretti
Rosella
R
Gallinella
Bruno
B
La Torre
Francesco
F
Anzini
Maurizio
M
Patrignani
Paola
P