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. 2014 Sep 26;19(10):15361–15373. doi: 10.3390/molecules191015361

Table 1.

Characteristics of some bioreductive prodrugs [2].

Prodrug Chemical Structure Chemical Class Mechanism of Action * Mechanism of Cytotoxicity One-Electron Reductases Two-Electron Reductases KO2 (µM)
TPZ graphic file with name molecules-19-15361-i001.jpg Aromatic N-oxide 1, 3 [R.] *** Complex DNA damage CYPOR ** iNOS ** NQO1 ** ±1
SN30000 graphic file with name molecules-19-15361-i002.jpg Aromatic N-oxide 1, 3 [R.] *** Complex DNA damage CYPOR ** ---- ±1
AQ4N graphic file with name molecules-19-15361-i003.jpg Aliphatic N-oxide 2, 5 [Y] *** Topoisomerase II inhibition iNOS ** CYP3A4 ** CYP2S1 ** ----
EP-0152R plus CB1954 graphic file with name molecules-19-15361-i004.jpg Nitro 1/2, 4, 5, 6 [Y, Z] *** DNA interstrand crosslink CYPOR ** iNOS ** NQO1 ** NQO2 ** ----
EO9 graphic file with name molecules-19-15361-i005.jpg Quinone 1, 4 [X, Y] *** DNA interstrand crosslink CYPOR ** NQO1 ** ----

* Reaction numbers: 1: one electron reduction generates a prodrug radical; 2: fragmentation of the prodrug radical generates radical R. and cytotoxin D; 3: one electron reduction of the prodrug radical; 4 and 5: subsequent reduction of the two electron reduction produces X; 6: two-electron reduction of the prodrug generates product X; ** CYPOR-NADPH–cytochrome P450 reductase, iNOS-inducible nitric oxide synthase, NQO-NAD(P)H dehydrogenase [quinone], CYP-cytochrome P 450; *** Active cytotoxins (R·, X, Y, Z). All abbreviations refer to reference [2] Figure 2A.