Scheme 1.
Synthesis of thiazolidine-2-thione derivatives 4a-4d.
i: H2SO4, 0°C; ii: KOH, EtOH, 40°C; iii: NaOH, EtOH, 50°C (4a, 4b); NaOH, EtOH, CuI, 80°C (4c, 4d).
Scheme 2.
Synthesis of thiazolidine-2-thione derivatives 6a-6k.
i. TEA, CH2Cl2, 0°C; ii. TEA, THF, R.T.
Table 1.
In vitro XO inhibitory potency of thiazolidine-2-thione derivatives.
Fig 1.
Kinetic analysis of compound 6k inhibited of XO activity.
(a) Lineweaver-Burk plots analysis, c(XO) = 55 U/L, c(compound 6k) = 0, 5, 10, and 20 μmol/L, c(xanthine) = 0.25, 0.5, 1.0, and 2.0 mmol/L. (b/c) Ki and Kis of compound 6k, Ki and Kis were obtained from secondary plots of the slopes of the Lineweaver-Burk plots and the apparent 1/Vmax versus the inhibitor concentrations, respectively.
Fig 2.
Molecular docking of thiazolidine-2-thione and compound 6k within the binding pocket of XDH.
(a) The binding modes of thiazolidine-2-thione with XDH (PDB: 3ETR), and the hydrogen bonds of thiazolidine-2-thione with the key amino acid residues in XDH; (b) The binding modes of compounds 6k with XDH, and hydrogen bonds of compound 6k with the key amino acid residues in XDH.