Antimycobacterial activity of new 3,5-disubstituted 1,3,4-oxadiazol-2(3H)-one derivatives. Molecular modeling investigations

被引：44

作者：

Zampieri, Daniele ^{[1
]}

Mamolo, Maria Grazia ^{[1
]}

Laurini, Erik ^{[1
]}

Fermeglia, Maurizio ^{[2
]}

Posocco, Paola ^{[2
]}

Pricl, Sabrina ^{[2
]}

Banfi, Elena ^{[3
]}

Scialino, Giuditta ^{[3
]}

Vio, Luciano ^{[1
]}

机构：

[1] Univ Trieste, Dept Pharmaceut Sci, I-34127 Trieste, Italy

[2] Univ Trieste, Dept Chem Environm & Raw Mat Engn, I-34127 Trieste, Italy

[3] Univ Trieste, Dept Life Sci, I-34127 Trieste, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 13期

关键词：

3,5-Disubstituted 1,3,4-oxadiazol-2(3H)-one derivatives; Antimycobacterial activity; Molecular modeling; MULTIDRUG-RESISTANT TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; CONTINUUM SOLVENT; GENERALIZED BORN; DRUG-RESISTANCE; ATOMIC CHARGES; MANNICH-BASES; FREE-ENERGIES; RESP MODEL; DYNAMICS;

D O I：

10.1016/j.bmc.2009.04.055

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 H37Rv. 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 14 alpha-demethylase in the sterol biosynthesis pathway as the calculated free energy of binding were in agreement with the corresponding MIC values. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：4693 / 4707

页数：15

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