Design, synthesis, antibacterial and QSAR studies of benzimidazole and imidazole chloroaryloxyalkyl derivatives.
In view of obtaining some potential antibacterial compounds, we have described synthesis of some chloroaryloxyalkyl imidazole and benzimidazole derivatives. The relevant step in the synthetic sequence was the initial condensation of 4-chloro or 2,4-dichlorophenol with 1, n-dibromoalkanes (n=2, 4, 5) to provide compounds 3a-f in sufficient yields. The subsequent condensation of 3a-f with some imidazole derivatives and benzimidazole afforded products 4a-l and 5a-e in good yields. Some of compounds 4a-l as well as 5a-e were tested in vitro against Salmonella typhi O-901 and Staphylococcus aureus A 15091. Compounds 4a and 4c showed considerable bactericidal activities against tested bacteria. Compound 4b showed significant activity against S. aureus A 15091 but was inactive against S. typhi O-901. Other compounds showed intermediate activities against S. aureus A 15091 but most of them were inactive against S. typhi O-901. Semiempirical AM1 calculations showed that negative electrostatic potentials around oxygen of the phenoxy and nitrogen of the imidazole moieties have direct effect on the antibacterial activity towards S. aureus A 15091. In QSAR analysis, different electronic, topologic, functional groups and physicochemical descriptors were calculated for each molecule and a three parametric equation was found between the logMIC and HOMO energy, hydration energy and number of primary carbon atoms of the molecules.
Khalafi-Nezhad
A
A
Department of Chemistry, Faculty of Science, Shiraz University, Shiraz 71454, Iran.
Soltani Rad
M N
MN
Mohabatkar
H
H
Asrari
Z
Z
Hemmateenejad
B
B
D000478:Alkylation; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D002712:Chlorides / Q000737:chemistry*; D015195:Drug Design; D007093:Imidazoles / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D021281:Quantitative Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D001562:Benzimidazoles; D002712:Chlorides; D007093:Imidazoles; C029899:imidazole; C031000:benzimidazole