title: Antimycobacterial activity of new 3,5-disubstituted 1,3,4-oxadiazol-2(3H)-one derivatives. Molecular modeling investigations.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, Piazzale Europa 1, University of Trieste, Trieste, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Zampieri
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Mamolo
authors.forename: Erik
authors.initials: E
authors.lastname: Laurini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fermeglia
authors.forename: Paola
authors.initials: P
authors.lastname: Posocco
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pricl
authors.forename: Elena
authors.initials: E
authors.lastname: Banfi
authors.forename: Giuditta
authors.initials: G
authors.lastname: Scialino
authors.forename: Luciano
authors.initials: L
authors.lastname: Vio
mesh_terms: 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
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D065607:Cytochrome P-450 Enzyme Inhibitors; D010069:Oxadiazoles; D003577:Cytochrome P-450 Enzyme System; D058886:Sterol 14-Demethylase