A click chemistry approach to explore a new scaffold for potential antitubercular agents

Our ongoing researches are aimed to discover novel potential antitubercular agents targeting siderophore biosynthesis. Previously, we identified compound I (Chart 1) as an MbtI (Mycobacterium turberculosis Salicylate Synthase) inhibitor (% residual enzymatic activity = 18.2) and we decided to gain an insight into the biological relevance of the heterocycle. Therefore, we initially substituted the furan with the triazole ring, privileging the brevity and the versatility of the synthetic pathway. Considering the activity of compound I and the related compounds, we designed and synthesized some new triazole derivatives (1a-d and 2a-d, Chart 1), bearing opportune substituents. The two regioisomers obtained from each cycloaddition reaction were isolated and tested as MbtI inhibitors. The results will be discussed.