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 (CC50 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.

Biava, M., PORRETTA G., C., Poce, G., Battilocchio, C., Alfonso, S., DE LOGU, A., et al. (2010). Identification of a novel pyrrole derivative endowed with antimycobacterial activity and protection index comparable to that of the current antitubercular drugs streptomycin and rifampin. BIOORGANIC & MEDICINAL CHEMISTRY, 18(22), 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

MANETTI, FABRIZIO;BOTTA, MAURIZIO
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 (CC50 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.
Biava, M., PORRETTA G., C., Poce, G., Battilocchio, C., Alfonso, S., DE LOGU, A., et al. (2010). Identification of a novel pyrrole derivative endowed with antimycobacterial activity and protection index comparable to that of the current antitubercular drugs streptomycin and rifampin. BIOORGANIC & MEDICINAL CHEMISTRY, 18(22), 8076-8084 [10.1016/j.bmc.2010.09.006].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/22530
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