Tumour inhibitory triazenes: Structural requirements for an active metabolite

Dopamine- and tyramine-based derivatives of triazenes: Activation by tyrosinase and implications for prodrug design

“…Inspection of the HPLC traces of the reaction mixtures of the tyrosinase catalysed reactions revealed that triazenes 5 were rapidily converted to a metabolite that did not correspond either to the appropriate monomethyltriazene 4 or its aniline decomposition product [12]. To gain some insight to the structure of this metabolite, an LC-MS study of the reaction mixtures was performed.…”

“…Among all the chemotherapeutic agents tested against this malignancy, DTIC is the most active single agent and thus considered the reference drug [10,11]. Related 1-aryl-3,3-dimethyltriazenes, 3, (see Scheme 1) are also documented as anticancer drugs, but with reduced selectivity for tumour cells [12,13].…”

“…The biological action of DTIC and the dimethyltriazenes, 3, is a consequence of their capacity to alkylate DNA and RNA via the corresponding monomethyltriazene 4 following metabolic oxidation by cytochrome P450 enzymes (Scheme 1) [12,14,15].…”

Formulation of Dacarbazine-loaded Cubosomes. Part III. Physicochemical Characterization

“…Thirdly, the drug is light sensitive and unstable. Fourthly, DTIC is myelosuppressive, and its use in combination therapy has been further limited by its short half-life (11). One promising strategy to overcome these limitations is to encapsulate this drug using nanocarriers or nanoparticulate systems intended for controlled drug delivery.…”

3-(4-Carbamoylphenyl)-1-methyltriazene 1-oxide

“…In establishing the structural requirements for anti-tumour activity of this class of compounds, we investigated 3-(4-carbamoylphenyl)-1-methyltriazene loxide [(Ib), R = -CONH2: CB 10-339 (Connors, Goddard, Merai, Ross & Wilman, 1976)] and showed it to be active against the TLX/5 lymphoma and the AdjPC6/A plasmacytoma (Wilman, 1985). It has also * To whom correspondence should be addressed.…”