Synthesis, thymidine phosphorylase inhibition and molecular modeling studies of 1,3,4-oxadiazole-2-thione derivatives

•Efficient synthesis of 1,3,4-oxadiazole-2-thione derivatives.•Thymidine phosphorylase inhibition studies.•Molecular docking studies for binding mode investigations.•Compound 6 bearing 4-hydroxyphenyl group was found to be the most active.

Thymidine phosphorylase (TP) inhibitors have attracted great attention due to their ability to suppress the tumors formation. In our ongoing research, a series of 1,3,4-oxadiazole-2-thione (1–12) has been synthesized under simple reaction conditions in good to excellent yields (86–98%) and their TP inhibition potential has also been evaluated. The majority of synthesized compounds showed moderate thymidine phosphorylase inhibitory activity with IC50 values ranging from 38.24 ± 1.28 to 258.43 ± 0.43 μM, and 7-deazaxanthine (7DX) was used as a reference compound (IC50 38.68 ± 4.42). The TP activity was very much dependent on the C-5 substituents; among this series the compound 6 bearing 4-hydroxyphenyl group was found to be the most active with IC50 38.24 ± 1.28 μM. Molecular docking studies revealed their binding mode.

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