Identification of 1,2,4-triazoles as new thymidine phosphorylase inhibitors: Future anti-tumor drugs.

07:00 EST 4th January 2019 | BioPortfolio

Summary of "Identification of 1,2,4-triazoles as new thymidine phosphorylase inhibitors: Future anti-tumor drugs."

Thymidine phosphorylase (TP) is over expressed in several solid tumors and its inhibition can offer unique target suitable for drug discovery in cancer. A series of 1,2,4-triazoles 3a-3l has been synthesized in good yields and subsequently inhibitory potential of synthesized triazoles 3a-3l against thymidine phosphorylase enzyme was evaluated. Out of these twelve analogs five analogues 3b, 3c, 3f, 3l and 3l exhibited a good inhibitory potential against thymidine phosphorylase. Inhibitory potential in term of IC values were found in the range of 61.98 ± 0.43 to 273.43 ± 0.96 μM and 7-Deazaxanthine was taken as a standard inhibitor with IC = 38.68 ± 4.42 μM. Encouraged by these results, more analogues 1,2,4-triazole-3-mercaptocarboxylic acids 4a-4g were synthesized and their inhibitory potential against thymidine phosphorylase was evaluated. In this series, six analogues 4b-4g exhibited a good inhibitory potential in the range of 43.86 ± 1.11-163.43 ± 2.03 μM. Angiogenic response of 1,2,4-triazole acid 4d was estimated using the chick chorionic allantoic membrane (CAM) assay. In the light of these findings, structure activity relationship and molecular docking studies of selected triazoles to determine the key binding interactions was discussed. Docking studies demonstrate that synthesized analogues interacted with active site residues of thymidine phosphorylase enzyme through π-π stacking, thiolate and hydrogen bonding interactions.


Journal Details

This article was published in the following journal.

Name: Bioorganic chemistry
ISSN: 1090-2120
Pages: 209-220


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Medical and Biotech [MESH] Definitions

The enzyme catalyzing the transfer of 2-deoxy-D-ribose from thymidine to orthophosphate, thereby liberating thymidine. EC

The active form of GLYCOGEN PHOSPHORYLASE that is derived from the phosphorylation of PHOSPHORYLASE B. Phosphorylase a is deactivated via hydrolysis of phosphoserine by PHOSPHORYLASE PHOSPHATASE to form PHOSPHORYLASE B.

The inactive form of GLYCOGEN PHOSPHORYLASE that is converted to the active form PHOSPHORYLASE A via phosphorylation by PHOSPHORYLASE KINASE and ATP.

An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC

An enzyme that deactivates glycogen phosphorylase a by releasing inorganic phosphate and phosphorylase b, the inactive form. EC

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