A hit optimization procedure based on isosteric and bioisosteric replacement of decorating groups at both the N1 and the C5 phenyl rings of 1,5-diarylpyrroles led to identification of 4-((1-(4-fluorophenyl)-2-methyl-5- (4-(methylthio)phenyl)-1H-pyrrol-3-yl)methyl)thiomorpholine that is characterized by a very high activity toward both Mycobacterium tuberculosis 103471 and H37Rv strains (MIC values of 0.125 μg/mL), and a safe profile in terms of cytotoxicity (CC 50 of >128 μg/mL) and protection index (>1000). Antitubercular activity and protection index of the new compound are comparable to those found for the current antitubercular drugs streptomycin and rifampin. © 2010 Elsevier Ltd. All rights reserved.
Identification of a novel pyrrole derivative endowed with antimycobacterial activity and protection index comparable to that of the current antitubercular drugs streptomycin and rifampin / Biava, Mariangela; Porretta, Giulio Cesare; Poce, Giovanna; Battilocchio, Claudio; Alfonso, Salvatore; A., De Logu; Nadia, Serra; Fabrizio, Manetti; Maurizio, Botta. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 18:22(2010), pp. 8076-8084. [10.1016/j.bmc.2010.09.006]
Identification of a novel pyrrole derivative endowed with antimycobacterial activity and protection index comparable to that of the current antitubercular drugs streptomycin and rifampin
BIAVA, Mariangela;PORRETTA, Giulio Cesare;POCE, Giovanna;BATTILOCCHIO, CLAUDIO;ALFONSO, SALVATORE;
2010
Abstract
A hit optimization procedure based on isosteric and bioisosteric replacement of decorating groups at both the N1 and the C5 phenyl rings of 1,5-diarylpyrroles led to identification of 4-((1-(4-fluorophenyl)-2-methyl-5- (4-(methylthio)phenyl)-1H-pyrrol-3-yl)methyl)thiomorpholine that is characterized by a very high activity toward both Mycobacterium tuberculosis 103471 and H37Rv strains (MIC values of 0.125 μg/mL), and a safe profile in terms of cytotoxicity (CC 50 of >128 μg/mL) and protection index (>1000). Antitubercular activity and protection index of the new compound are comparable to those found for the current antitubercular drugs streptomycin and rifampin. © 2010 Elsevier Ltd. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
