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