Synthesis of carbazole derivatives for testing as antibacterial agents

The bacterial DNA sliding clamp, called β-clamp, is one of the key proteins involved in DNA replication. The clamp encircles DNA and increases the rate of polymerase processivity. An inhibition of the clamp will inhibit DNA replication, induce SOS response and potentially lead to cell death. Carbazoles are important scaffolds in drug development and are utilized in several anti-inflammatory agents. Yin. et al have proved that such structures could bind to the β-clamp and be potential guides to new antibacterial agents. An issue with these compounds is that they have limited cell activity. A potential way into the cell can be through the iron transport system. This may be achieved by including structural elements that are common in naturally occurring iron-chelating sideophores, such as catechols. This poster presents our work towards new carbazole derivatives, including a compound with a catechol-containing dopamine sidechain. In a central amide coupling step, different coupling reagents have been tested and evaluated in terms of efficiency, hazards and costs.