NBGNU: a hypoxia-activated tripartite combi-nitrosourea prodrug overcoming AGT-mediated chemoresistance

Aim: A hypoxia-activated combi-nitrosourea prodrug, N-(2-chloroethyl)-N'-2-(2-(4-nitrobenzylcarbamate)-O6-benzyl-9-guanine)ethyl-N-nitrosourea (NBGNU), was synthesized and evaluated for its hypoxic selectivity and anticancer activity in vitro. Results: The prodrug was designed as a tripartite molecule consisting of a chloroethylnitrosourea pharmacophore to induce DNA interstrand crosslinks (ICLs) and an O6-benzylguanine analog moiety masked by a...