Design and Synthesis of 2-Arylbenzimidazoles and Evaluation of Their Inhibitory Effect against Chlamydia pneumoniae

Abstract

Chlamydia pneumoniae is an intracellular bacterium that responds poorly to antibiotic treatment. Insufficient antibiotic usage leads to chronic infection, which is linked to disease processes of asthma, atherosclerosis, and Alzheimer's disease. The Chlamydia research lacks genetic tools exploited by other antimicrobial research, and thus other approaches to drug discovery must be applied. A set of 2-arylbenzimidazoles was designed based on our earlier findings, and 33 derivatives were synthesized. Derivatives were assayed against C. pneumoniae strain CWL-029 in an acute infection model using TR-FIA method at a concentration of 10 μM, and the effects of the derivatives on the host cell viability were evaluated at the same concentration. Fourteen compounds showed at least 80% inhibition, with only minor changes in host cell viability. Nine most potential compounds were evaluated using immunofluorescence microscopy on two different strains of C. pneumoniae CWL-029 and CV-6. The N-[3-(1H-benzimidazol-2-yl)phenyl]-3-methylbenzamide (42) had minimal inhibitory concentration (MIC) of 10 μM against CWL-029 and 6.3 μM against the clinical strain CV-6. This study shows the high antichlamydial potential of 2-arylbenzimidazoles, which also seem to have good characteristics for lead compounds.

Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro

“…The antichlamydial assays were performed by an immunofluorescence method on a 24-well plate, quantifying the number of chlamydial inclusions in infected HL cells using a Chlamydia-specific anti-LPS antibody, as described earlier in Salin et al 31 and Keurulainen et al 32 The antichlamydial effect of compound combinations was assayed by using a checkerboard method, with a single replicate. 33 Combinations were chosen, based on the activity results from dose-response experiments for single agents, and on each of the combination plates, the compounds were also present alone.…”

Microwave-assisted conversion of aromatic heterocyclic nitriles to various heterocyclic molecules

“…These types of heterocyclic compounds exhibit antitumor (8,9) anti-inflammatory (10,11), antibacterial (12), antiviral (13), and antimicrobial (14) activities. Since this investigation deals with a new approach to synthesize these medicinally important heterocyclic compounds, it is essential to review the procedures reported in literature.…”

Synthesis and antifungal activity of novel 2,5-disubstituted-1,3,4-oxadiazoles containing benzimidazole moiety

“…On the other hand, benzimidazole derivatives also exhibit a broad spectrum of biological activities, such as antifungal, 7) antibacterial, 8) antiviral, 9) antitumor 10) and antiparasitic 11) activities, which are important substances in agricultural and pharmaceutical elds. Among benzimidazole fungicides, carbendazim, benomyl and thiabendazole are still used in fungicide market due to their high e ciency, broad spectrum and good systemic property.…”