Inhibitory effects of arylcoumarin derivatives on Bacteroides fragilisd‑lactate dehydrogenase

Bacteroides fragilis is an anaerobic bacterium naturally hosted in the human colon flora. B. fragilisd‑lactate dehydrogenase (Bfd‑LDH) is an important enzyme which catalyzes the conversion of d‑lactate to pyruvate and regulates anaerobic glycolysis. In this study Bfd‑LDH has been targeted for structure based drug design. B. fragilisd‑lactate dehydrogenase has been expressed, purified and inhibitory activities of 25 coumarin derivatives previously synthetize for their antioxidant activity were evaluated. Among the 25 coumarin derivatives, compound 6a, 5l, and 6b exhibited the highest inhibitory activity with IC50 values of 0,47 μM, 0,57 μM ve 0,057 μM, respectively. The results indicate that the mechanism by which 6a, 5l and 6b coumarin derivatives inhibit Bfd‑LDH by reversible non-competitive inhibition. Docking experiments were carried out to further explain the results and compare the theoretical and experimental affinity of these compounds to the Bfd‑LDH protein. According to docking results, all coumarins bind to the site occupied by pyruvate and the nicotinamide ring of NADH. •d‑Lactate dehydrogenase was obtained in high purity.•6a, 5l, and 6b coumarin derivatives exhibited the highest inhibitory activity with IC50 values of 0,47 μM, 0,57 μM ve 0,057 μM, respectively.•6a, 5l and 6b coumarin derivatives inhibit Bfd‑LDH via a mechanism that is reversible non-competitive inhibition.•The Ki values for 6a, 5l, and 6b coumarin derivatives were identified as 0.4532 μM, 0.5183 μM, and 0.3603 μM, respectively.•Docking studies clarified whether coumarin derivatives interact with active residues of the enzyme.