New Anthracenedione Derivatives with Improved Biological Activity by Virtue of Stable Drug− DNA Adduct Formation

…, KG Watson, A Nudelman, A Rephaeli…

Index: Mansour, Oula C.; Evison, Benny J.; Sleebs, Brad E.; Watson, Keith G.; Nudelman, Abraham; Rephaeli, Ada; Buck, Damian P.; Collins, J. Grant; Bilardi, Rebecca A.; Phillips, Don R.; Cutts, Suzanne M. Journal of Medicinal Chemistry, 2010 , vol. 53, # 19 p. 6851 - 6866

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Citation Number: 16

Abstract

Mitoxantrone is an anticancer agent that acts as a topoisomerase II poison, however, it can also be activated by formaldehyde to form DNA adducts. Pixantrone, a 2-aza- anthracenedione with terminal primary amino groups in its side chains, forms formaldehyde- mediated adducts with DNA more efficiently than mitoxantrone. Molecular modeling studies indicated that extension of the “linker” region of anthracenedione side arms would allow ...