Structure-activity relationship studies and bioactivity evaluation of 1,2,3-triazole containing analogues as a selective sphingosine kinase-2 inhibitors.

ABSTRACT: Sphingosine kinase (SphK) is primarily responsible for the production of Sphingosine-1-phosphate (S1P) that plays an important role in many biological and pathobiological processes including cancer, inflammation, neurological and cardiovascular disorders. Most research has focused on developing inhibitors of SphK1 rather than inhibitors of the other isoform SphK2 which has great importance in several pathophysiologic pathways. Exploration of new analogues for improving the potency and selectivity of SphK2 inhibitors is critical. We now have designed, synthesized, and evaluated eighteen new 1,2,3-triazole analogues for their SphK2 inhibitory activity using a ADP-Glo kinase assay, and explored their in vivo anti-tumor bioactivity. Several compounds including 21c, 21e, 21g, 25e-h, 29a-c have

SUBMITTER: Tangadanchu VKR 

PROVIDER: S-EPMC8781238 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature