Natural products as privileged structures for the conception of novel antimycobacterial agents

Natural products play a major role in drug discovery, as a unique source of original structures, which can provide models for future drug design. In the field of antitubercular agents, the lichen dibenzofuran derived secondary metabolite usnic acid has been shown to display an interesting activity, but its weak potency did not permit its further development as an antimycobacterial drug. Also, the benzo[b]pyran system appears as a privileged structure, present in numerous bioactive natural product. Consequently, we focused our recent research on natural product-like hybrids, containing a pyran ring fused onto dibenzofuran basic core, as novel potential antitubercular agents. Among the series of compounds recently synthesized, 3,3-diméthyl-3H-benzofuro[3,2-f]-benzopyran (1) and its dihydro derivative 2 exhibit promising antitubercular activities [1], with a MIC₉₅ value of 10µg/mL against several strains of Mycobacterium tuberculosis. In terms of structure activity relationships, replacement of the furan oxygen atom by a sulfur (thiophen series) (3) result in a significant decrease of the antimycobacterial activity.

Reference: 1. Prado, S. et al. (2006) Bioorg. Med. Chem. 14:5423–5428.