Synthesis and biological evaluation of novel isoellipticine derivatives and salts

Miller, Charlotte M.; O’Sullivan,  Elaine C.; Devine, Ken J.; McCarthy, Florence O.

Synthesis and biological evaluation of novel isoellipticine derivatives and salts

Files

C2OB26181Bpreprint2.pdf(294.26 KB)

Accepted Version

Date

2012-08-24

Authors

Miller, Charlotte M.

O’Sullivan, Elaine C.

Devine, Ken J.

McCarthy, Florence O.

Publisher

Royal Society of Chemistry

Published Version

https://doi.org/10.1039/C2OB26181B

Abstract

Synthesis of novel 7-substituted isoellipticines and isoellipticinium salts is described, with optimisation of routes, representing a new class of anti-cancer agent. Initial assessment of biological activity using a topoisomerase II decatenation assay and NCI screening highlighted strong anti-cancer activity, further developed in a panel of isoellipticinium salts. Interestingly, low correlation between results of the topoisomerase II decatenation assay and NCI screen throughout the panel suggest that topo II is not the most important biological target with respect to anti-cancer activity in this new class of compounds. Results also suggest that solubility is not the limiting factor in activity of the isoellipticinium salts. Overall, 20 novel ellipticine analogues were prepared and full anti-cancer profiling was completed for 13 isoellipticine derivatives and salts. Two compounds display significant specificity towards CNS cancer cell lines and are lead compounds for future development.

Keywords

Isoellipticine , Ellipticine , Cancer , Topoisomerase

Citation

Miller, C. M., O'Sullivan, E. C., Devine, K. J. and McCarthy, F. O. (2012) 'Synthesis and biological evaluation of novel isoellipticine derivatives and salts', Organic and Biomolecular Chemistry, 10(39), pp. 7912-7921. doi: https://doi.org/10.1039/C2OB26181B