244151-84-6Relevant articles and documents
Pyrrolobenzimidazoles Linked to Heterocycles and Peptides. Design of DNA Base Pair Specific Phosphate Hydrolyzing Agents and Novel Cytotoxic Agents
Ghodousi, Arman,Huang, Xiaofen,Cheng, Zheng,Skibo, Edward B.
, p. 90 - 100 (2004)
Work in this laboratory has been involved with the design of aziridinyl quinone-based cancer drugs (PBIs) capable of both recognizing the DNA major groove and cleaving the phosphate backbone upon reduction to the hydroquinone. The hydroquinone species rec
Design of highly active analogues of the pyrrolo[1,2-a]benzimidazole antitumor agents
Craigo, William A.,LeSueur, Benjamin W.,Skibo, Edward B.
, p. 3324 - 3333 (2007/10/03)
The pyrrolo[1,2-a]benzimidazole (PBI) reductive alkylating agents have been investigated in this laboratory since their discovery in the late 1980s. Of all the structural modifications of the PBIs investigated so far, the variation of the 3-substituent has the greatest influence on cytotoxicity, toxicity, and in vivo antitumor activity. In the present study, we prepared both the R and S enantiomers of nitrogen-containing 3-substituents possessing hydrogen-bonding capability as well as varying basicity. The rationale was to take advantage of stereoselective DT-diaphorase reductive activation as well as hydrogen bonding in the DNA major groove. As a result of these studies, analogues were discovered possessing among the highest hollow fiber tumor assay scores observed in hundreds of natural and synthetic antitumor agents. Our findings indicate that a relatively basic 3-substituent is required for outstanding PBI cytotoxicity but that the importance of using pure enantiomers is still open to study.
