Evaluation of heteroatom-rich derivatives as antitubercular agents with InhA inhibition properties

Two series of heterocyclic compounds derived from 3-acetyl-4-hydroxy-6-methyl-2 H -pyran-2-one (DHA) and 2-acetylbutyrolactone have been synthesized and characterized. The compounds were evaluated for their activities against Mycobacterium tuberculosis strain, and as inhibitors of InhA, a key enzyme involved in the type II fatty acid biosynthesis pathway of M. tuberculosis . Among the tested compounds, one DHA derivative, compound 2 , showed promising activity against both mycobacteria and InhA. Docking studies were also carried out and give some new structure-activity trends compatible with current structural knowledge.