Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR

Elrashied A E Garelnabi, Dimitrios Pletsas, Li Li, Konstantinos Kiakos, Nazira Karodia, John A. Hartley, Roger M. Phillips, Richard T. Wheelhouse

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)965-968
Number of pages4
JournalACS Medicinal Chemistry Letters
Volume3
Issue number12
Early online date18 Sep 2012
DOIs
Publication statusPublished - 13 Dec 2012
Externally publishedYes

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temozolomide
Prodrugs
Ions
DNA Mismatch Repair
Alkylating Agents
DNA
Methyltransferases
Acids
Repair
O-(6)-methylguanine

Cite this

Garelnabi, E. A. E., Pletsas, D., Li, L., Kiakos, K., Karodia, N., Hartley, J. A., ... Wheelhouse, R. T. (2012). Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR. ACS Medicinal Chemistry Letters, 3(12), 965-968. https://doi.org/10.1021/ml300132t
Garelnabi, Elrashied A E ; Pletsas, Dimitrios ; Li, Li ; Kiakos, Konstantinos ; Karodia, Nazira ; Hartley, John A. ; Phillips, Roger M. ; Wheelhouse, Richard T. / Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR. In: ACS Medicinal Chemistry Letters. 2012 ; Vol. 3, No. 12. pp. 965-968.
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Garelnabi, EAE, Pletsas, D, Li, L, Kiakos, K, Karodia, N, Hartley, JA, Phillips, RM & Wheelhouse, RT 2012, 'Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR', ACS Medicinal Chemistry Letters, vol. 3, no. 12, pp. 965-968. https://doi.org/10.1021/ml300132t

Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR. / Garelnabi, Elrashied A E; Pletsas, Dimitrios; Li, Li; Kiakos, Konstantinos; Karodia, Nazira; Hartley, John A.; Phillips, Roger M.; Wheelhouse, Richard T.

In: ACS Medicinal Chemistry Letters, Vol. 3, No. 12, 13.12.2012, p. 965-968.

Research output: Contribution to journalArticle

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AU - Kiakos, Konstantinos

AU - Karodia, Nazira

AU - Hartley, John A.

AU - Phillips, Roger M.

AU - Wheelhouse, Richard T.

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KW - cancer

KW - DNA

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