Conformation study of 2-arylbenzimidazoles as inhibitors of Chlamydia pneumoniae growth.
Chlamydia pneumoniae is a worldwide cause of various respiratory track diseases ranging from asymptomatic pharyngeal infection to severe, sometimes fatal pneumonia. We have previously identified 2-arylbenzimidazoles as highly active antichlamydial compounds. In this work the importance of conformational effects on the structure-activity relationship of these compounds was studied. To simplify calculations, properly substituted N-phenylbenzamides, or the corresponding heterocyclic compounds, and 2-arylbenzimidazoles were used as model compounds. They were energy minimized and the energy differences between certain conformations were calculated. The main finding was that the compounds which can more easily adopt a non-planar conformation show higher bioactivity. This finding can be utilized in designing new derivatives or in constructing a pharmacophore model.
Division of Pharmaceutical Chemistry, Faculty of Pharmacy, Biocenter Viikki, PO Box 56 (Viikinkaari 5 E), FI-00014 University of Helsinki, Finland.
Antti
A
Siiskonen
Leena
L
Keurulainen
Olli
O
Salin
Paula
P
Kiuru
Leena
L
Pohjala
Pia
P
Vuorela
Jari
J
Yli-Kauhaluoma
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology; D016993:Chlamydophila pneumoniae / Q000187:drug effects* / Q000254:growth & development; D050296:Microbial Viability / Q000187:drug effects; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D001562:Benzimidazoles