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New methodology for benzimidazoles

We have developed methodologies to prepare novel 2-substituted N-alkoxybenzimidazoles with various types of substituents, unavailable by traditional benzimidazole syntheses. The methods are applicable to a very wide potential diversity of structures. A number of these have provided new compounds which have shown activity against HIV or cancer cell lines. We have also shown this can be used for the generation of novel symmetrical dimeric systems, of the two general types shown.

Research workers contributing to this project: Kanan El-Wahedy, Colin Loyns, Jonny Procter.

Oligomeric Benzimidazoles

A number of dimeric (and oligomeric) benzimidazoles feature highly amongst sequence-selective DNA minor groove binders (an example from our own modelling is shown bound to DNA (left)). Such heterocyclic systems have been attracting attention because they potentially offer a wide array of structural variability, and thus the opportunity to develop and fine tune new DNA/RNA binding agents.

We have developed routes to several new classes of oligobenzimidazole and are evaluating this chemistry for further diversity and evaluating the structural features for DNA binding efficacy and selectivity.

This has identified several new types of DNA binding ligand types.

Research workers contributing to this project: Shatha Al-Aqeel, Aqeel Ahmad, Kanan El-Wahedy.

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