Title

Synthesis of an aminopropyl analog of the experimental anticancer drug tallimustine, and activation of its 4-nitrobenzylcarbamoyl prodrug by nitroreductase and NADH

ACS Citation

Lee, M.; Simpson, J. E.; Woo, S.; Kaenzig, C.; Anlezark, G. M.; Eno-Amooquaye, E.; Burke, P. J. Synthesis of an aminopropyl analog of the experimental anticancer drug tallimustine, and activation of its 4-nitrobenzylcarbamoyl prodrug by nitroreductase and NADH. Bioorg. Med. Chem. Lett. 1997, 7, 1065-1070.

Abstract

Compound 1, an analog of tallimustine that contains an aminopropyl group at the C-terminus, and its 4-nitrobenzylcarbamoyl prodrug 2 have been prepared. Analog 1 binds preferentially to the minor groove of poly(dA-dT) over poly(dG-dC), and is cytotoxic against the growth of LS1747 and SW1116 human colon cancer cells, with IC50 values of 0.02 μM and 10.0 μM, respectively. The prodrug 2 is significantly less cytotoxic (2.3 and 22.9 μM, respectively) than the parent drug 1. However, in the presence of nitroreductase and NADH prodrug 2 is as active as compound 1.

Source Name

Bioorganic & Medicinal Chemistry Letters

Publication Date

1-1-1997

Volume

7

Issue

8

Page(s)

1287-1291

Document Type

Citation

Citation Type

Article