C2/C3-内双键对吡咯并[2,1-c][1,4]苯并二氮杂䓬细胞毒性和DNA结合反应性的影响。

Effect of C2/C3-endo unsaturation on the cytotoxicity and DNA-binding reactivity of pyrrolo[2,1-c][1,4]benzodiazepines.

作者信息

Gregson S J, Howard P W, Barcella S, Nakamya A, Jenkins T C, Kelland L R, Thurston D E

机构信息

CRC Gene Targeted Drug Design Research Group, School of Pharmacy and Biomedical Science, University of Portsmouth, Hants, UK.

出版信息

Bioorg Med Chem Lett. 2000 Aug 21;10(16):1849-51. doi: 10.1016/s0960-894x(00)00350-4.

DOI:10.1016/s0960-894x(00)00350-4

PMID:10969983

Abstract

A series of novel C2,C3-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) has been synthesised via cleavage of the N10-Alloc protecting group from appropriate precursors. Biophysical and biological evaluations show that the presence of C2/C3-endo unsaturation in the PBD C-ring enhances both DNA-binding reactivity and in vitro cytotoxic potency.

摘要

通过从合适的前体中裂解N10-Alloc保护基团，合成了一系列新型的C2,C3-内型不饱和吡咯并[2,1-c][1,4]苯并二氮杂卓（PBDs）。生物物理和生物学评估表明，PBD C环中C2/C3-内型不饱和的存在增强了DNA结合反应性和体外细胞毒性效力。