Design of new quinolin-2-one-pyrimidine hybrids as sphingosine kinases inhibitors.

ABSTRACT: Sphingosine-1-phosphate is now emerging as an important player in cancer, inflammation, autoimmune, neurological and cardiovascular disorders. Abundance evidence in animal and humans cancer models has shown that SphK1 is linked to cancer. Thus, there is a great interest in the development new SphK1 inhibitors as a potential new treatment for cancer. In a search for new SphK1 inhibitors we selected the well-known SKI-II inhibitor as the starting structure and we synthesized a new inhibitor structurally related to SKI-II with a significant but moderate inhibitory effect. In a second approach, based on our molecular modeling results, we designed new structures based on the structure of PF-543, the most potent known SphK1 inhibitor. Using this approach, we report the design, synthesis and biol

SUBMITTER: Vettorazzi M 

PROVIDER: S-EPMC6954317 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature