Antimycobacterial activity of new 3,5-disubstituted 1,3,4-oxadiazol-2(3H)-one derivatives. Molecular modeling investigations.
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 reference strain of Mycobacterium tuberculosis H(37)Rv. Molecular modeling investigations were performed and showed that the active compounds possess all necessary features to target the protein active site of the mycobacterial cytochrome P450-dependent sterol 14alpha-demethylase in the sterol biosynthesis pathway as the calculated free energy of binding were in agreement with the corresponding MIC values.
Zampieri
Daniele
D
Department of Pharmaceutical Sciences, Piazzale Europa 1, University of Trieste, Trieste, Italy.
Mamolo
Maria Grazia
MG
Laurini
Erik
E
Fermeglia
Maurizio
M
Posocco
Paola
P
Pricl
Sabrina
S
Banfi
Elena
E
Scialino
Giuditta
G
Vio
Luciano
L
D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003198:Computer Simulation; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000502:physiology; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D058886:Sterol 14-Demethylase; D013816:Thermodynamics; D014376:Tuberculosis / Q000188:drug therapy
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D065607:Cytochrome P-450 Enzyme Inhibitors; D010069:Oxadiazoles; D003577:Cytochrome P-450 Enzyme System; D058886:Sterol 14-Demethylase