TY - JOUR
T1 - Synthesis and biological evaluation of novel isoellipticine derivatives and salts
AU - Miller, Charlotte M.
AU - O'Sullivan, Elaine C.
AU - Devine, Ken J.
AU - McCarthy, Florence O.
PY - 2012/10/21
Y1 - 2012/10/21
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84874964470
U2 - 10.1039/c2ob26181b
DO - 10.1039/c2ob26181b
M3 - Article
C2 - 22940706
AN - SCOPUS:84874964470
SN - 1477-0520
VL - 10
SP - 7912
EP - 7921
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
IS - 39
ER -
