Title

Synthesis and biological evaluation of selective phosphonate-bearing 1,2,3-triazole-linked sialyltransferase inhibitors

Publication Name

RSC Medicinal Chemistry

Abstract

The critical role of sialyltransferase (ST) enzymes in tumour cell growth and metastasis, as well as links to multi-drug and radiation resistance, has seen STs emerge as a target for potential antimetastatic cancer treatments. One promising class of ST inhibitors that improve upon the pharmacokinetic issues of previous inhibitors is the 1,2,3-triazole-linked transition-state analogues. Herein, we present the design and synthesis of a new generation of 1,2,3-triazole-linked sialyltransferase inhibitors, along with their biological evaluation demonstrating increased potency for phosphonate bearing compounds. The six most promising inhibitors presented in this work exhibited a greater number of binding modes for hST6Gal I over hST3Gal I, withKiranging from 3-55 μM. This work highlights phosphonate bearing triazole-linked compounds as a promising class of synthetically accessible ST inhibitors that warrant further investigation.

Open Access Status

This publication is not available as open access

Volume

12

Issue

10

First Page

1680

Last Page

1689

Funding Number

DP170101773

Funding Sponsor

National Computational Infrastructure

Share

COinS
 

Link to publisher version (DOI)

http://dx.doi.org/10.1039/d1md00079a