Antimycobacterial activity of new 3-substituted 5-(pyridin-4-yl)-3H-1,3,4-oxadiazol-2-one and 2-thione derivatives. Preliminary molecular modeling investigations.
3H-1,3,4-Oxadiazole-2-thione and 3H-1,3,4-oxadiazol-2-one derivatives were synthesized and tested for their in vitro antimycobacterial activity. Oxadiazolone derivatives showed an interesting antimycobacterial activity against the tested strain of Mycobacterium tuberculosis H(37)Rv, whereas the corresponding thione derivatives were devoid of activity. Molecular modeling investigations showed that the active compounds may interact at the active site of the mycobacterial cytochrome P450-dependent sterol 14alpha-demethylase in the sterol biosynthesis pathway and that their binding free energy values are in agreement with their MIC values.
Mamolo
Maria Grazia
MG
Department of Pharmaceutical Sciences, Piazzale Europa 1, University of Trieste, 34127 Trieste, Italy. mamolo@units.it
Zampieri
Daniele
D
Vio
Luciano
L
Fermeglia
Maurizio
M
Ferrone
Marco
M
Pricl
Sabrina
S
Scialino
Giuditta
G
Banfi
Elena
E
D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*
D000995:Antitubercular Agents