The isoprenoid derivative N⁶ -benzyladenosine CM223 exerts antitumor effects in glioma patient-derived primary cells through the mevalonate pathway.

ABSTRACT:

Background and purpose

N⁶ -Isopentenyladenosine (i6A) is a modified nucleoside exerting in vitro and in vivo antiproliferative effects. We previously demonstrated that the actions of i6A correlate with the expression and activity of farnesyl pyrophosphate synthase (FPPS), a key enzyme involved in the mevalonate (MVA) pathway, which is aberrant in brain cancer. To develop new anti-glioma strategies, we tested related compounds exhibiting greater activity than i6A.

Experimental approach

We designed and synthesized i6A derivatives characterized by the introduction of diverse chemical moieties in the N6 position of adenosine and tested for their efficacy in U87 cells and in primary glioma cultures, derived from patients. NMR-based structural analysis, molecular dockin

SUBMITTER: Ciaglia E 

PROVIDER: S-EPMC5481646 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature