Effects of Carnosic and Usnic Acid on Pentose Phosphate Pathway Enzymes: An Experimental and Molecular Docking Study

Abstract

Abstract6‐phosphogluconate dehydrogenase (6PGD) and Glucose‐6‐phosphate dehydrogenase (G6PD) are crucial enzymes involved in generating cellular reducing power. Modifying the balance of reduced NADPH is considered essential for cancer advancement and combined therapeutic strategies. Usnic acid (UA) is a physiologically active dibenzofuran derivative. Carnosic acid (CA) is a phenolic diterpene that has been isolated from several plants. This work evaluated the inhibitory effects of UA and CA on G6PD and 6PGD by in vitro tests. Molecular docking studies were employed to predict the mechanisms of inhibition. IC50 values for UA and CA were determined to be 49.50 μM and 77.00 μM for G6PD, and 69.30 μM and 57.75 μM for 6PGD, respectively. The Ki values for UA and CA were determined to be 35.01±7.69 μM and 43.46±10.48 μM for G6PD, and 104.87±11.86 μM and 31.17±2.55 μM for 6PGD, respectively. UA was identified as the most effective inhibitor against G6PD, whereas CA exhibited the best inhibitory activity against 6PGD, with estimated binding energies of −8.0 and −7.8 kcal/mol, respectively, in molecular docking studies. Ultimately, it was shown that the results obtained from in vitro and in silico methods in the study were strongly associated. These chemicals′ structure might assist in creating medications that focus on the pentose phosphate pathway.