QSAR MODELING OF ANTIMICROBIAL ACTIVITY OF SOME 2-SUBSTITUTED
BENZIMIDAZOLE DERIVATIVES
Sanja Ostoja Podunavac-Kuzmanović, Slobodan B. Gadzurić and Dragoljub D. Cvetković
Department of Applied and Engineering Chemistry, Faculty of Technology, University of Novi Sad, Serbia;
Abstract:
Because of their excellent activities, benzimidazole and its derivatives have a long history as antimicrobial agents.
Several thousands of benzimidazole analogs have been synthesized and screened for pharmacological activity. They are
of wide interest because of their diverse biological activity and clinical applications. These heterocyclic systems have
different activities as they can act as bacteriostats or bactericides, as well as fungicides and they are present in numerous
antiparasitic, antiprotozoal and antiviral drugs [1-3]. Some of 2-substituted benzimidazole derivatives were confirmed to
have a moderate in vitro anticancer activity, as well as some of them exhibited antitumor activity against human
hepatocellular carcinoma (HEPG2), human breast adenocarcinoma (MCF7) and human colon carcinoma (HCT 116) cell
lines [4].
In continuation of our studies on inhibitory activities of benzimidazole derivatives [5-7], in the present work we
examined the activity of different substituted 2-methyl and 2-aminobenzimidazoles against Gram-negative bacteria
Escherichia coli and studied the quantitative effect of molecular structure on inhibitory activity. The main objective was
to establish a quantitative structure-activity relationships (QSAR) and derive a high-quality model which would link the
structure of these compounds with their inhibitory activity.
The validity of the model has been established by the determination of suitable statistical parameters. The established
model was used to predict inhibitory activity of the benzimidazoles investigated and close agreement between
experimental and predicted values was obtained. The low residual activity and high cross-validated r2 values (r2CV)
observed indicated the predictive ability of the developed QSAR model. It indicates that the antibacterial activity of
series of 2-substituted benzimidazole derivatives can be successfully modeled using different molecular descriptors.
These results are part of the project No. 172012, supported by the Ministry of Science and Technological Development
of the Republic of Serbia.
References:
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[4] H. M.Refaat, Eur. J. Med. Chem. 45, 2949 (2010).
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