title: Design, synthesis, antibacterial and QSAR studies of benzimidazole and imidazole chloroaryloxyalkyl derivatives.
abstract: 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.
authors.affiliation: Department of Chemistry, Faculty of Science, Shiraz University, Shiraz 71454, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Khalafi-Nezhad
authors.forename: M N
authors.initials: MN
authors.lastname: Soltani Rad
authors.forename: H
authors.initials: H
authors.lastname: Mohabatkar
authors.forename: Z
authors.initials: Z
authors.lastname: Asrari
authors.forename: B
authors.initials: B
authors.lastname: Hemmateenejad
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D001562:Benzimidazoles; D002712:Chlorides; D007093:Imidazoles; C029899:imidazole; C031000:benzimidazole