title: Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR.
abstract: The imidazotetrazine ring is an acid-stable precursor and prodrug of highly reactive alkyl diazonium ions. We have shown that this reactivity can be managed productively in an aqueous system for the generation of aziridinium ions with 96% efficiency. The new compounds are potent DNA alkylators and have antitumor activity independent of the O6-methylguanine-DNA methyltransferase and DNA mismatch repair constraints that limit the use of Temozolomide.
authors.affiliation: School of Pharmacy, Institute of Cancer Therapeutics, and Chemical and Forensic Sciences, University of Bradford , Bradford BD7 1DP, U.K.
authors.forename: Elrashied A E
authors.initials: EA
authors.lastname: Garelnabi
authors.affiliation: School of Pharmacy, Institute of Cancer Therapeutics, and Chemical and Forensic Sciences, University of Bradford , Bradford BD7 1DP, U.K.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pletsas
authors.affiliation: School of Pharmacy, Institute of Cancer Therapeutics, and Chemical and Forensic Sciences, University of Bradford , Bradford BD7 1DP, U.K.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: UCL Cancer Institute , Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, U.K.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kiakos
authors.affiliation: School of Pharmacy, Institute of Cancer Therapeutics, and Chemical and Forensic Sciences, University of Bradford , Bradford BD7 1DP, U.K.
authors.forename: Nazira
authors.initials: N
authors.lastname: Karodia
authors.affiliation: UCL Cancer Institute , Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, U.K.
authors.forename: John A
authors.initials: JA
authors.lastname: Hartley
authors.affiliation: School of Pharmacy, Institute of Cancer Therapeutics, and Chemical and Forensic Sciences, University of Bradford , Bradford BD7 1DP, U.K.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Phillips
authors.affiliation: School of Pharmacy, Institute of Cancer Therapeutics, and Chemical and Forensic Sciences, University of Bradford , Bradford BD7 1DP, U.K.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Wheelhouse
keywords: 13C NMR; DNA; Imidazotetrazine; Temozolomide; aziridinium; cancer