Design, Synthesis and PASS Assisted Evaluation of Novel 2-Substituted Benzimidazole Derivatives as Potent Anthelimintics
Rajesh Kumar Goel.
Two series of compounds (AB and APB) bearing substituted phenoxy groups at 2-position of benzimidazole
nucleus through amino or phenyleneamino were synthesized and evaluated through PASS software for predicting the activity
spectrum of each compound. All compounds of both the series were predicted to have potent anthelmintic activity.
The activity of each compound was evaluated experimentally at the concentrations of 0.1, 0.2 and 0.5% in terms of mortality
time and paralysis time of the helminthes and was found to comply with the PASS predicted activity. In general, all
compounds of APB series were more potent than those of AB series probably due to the additional hydrophobic interactions
of the spacer phenyl ring in the APB series. The activity of all compounds was found to increase with increasing
concentration. The compound with p-chlorophenoxy moiety was the most active from the APB series (mortality time
5.7±0.4 min and paralysis time 3.1±0.3 min) and equipotent to albendazole (mortality time 5.4±0.1 min and paralysis time
2.8±0.2 min) at concentration of 0.2%. The o-chlorophenoxy analogs in both the series were found to be the least active of
all. Based on these results, a substituent capable of binding with the receptor through van der Waals and/or electronic interactions
at 4-position of the phenoxy ring in the compound is suggested to increase binding interaction leading to potent
Keywords: Benzimidazole, phenoxyacetic acid, anthelmintic, PASS, pharmacophore, intestinal worms, albendazole.
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