Bioorganic Chemistry 2015-06-01

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

Sohail Anjum Shahzad, Muhammad Yar, Marek Bajda, Lubna Shahzadi, Zulfiqar Ali Khan, Syed Ali Raza Naqvi, Sadaf Mutahir, Nasir Mahmood, Khalid Mohammed Khan

Index: Bioorg. Chem. 60 , 37-41, (2015)

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Abstract

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±0.43μM, 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±1.28μM. Molecular docking studies revealed their binding mode. Copyright © 2015 Elsevier Inc. All rights reserved.