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

doi:10.1021/ml300132t

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 journal › Article › peer-review

9 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 language	English
Pages (from-to)	965-968
Number of pages	4
Journal	ACS Medicinal Chemistry Letters
Volume	3
Issue number	12
Early online date	18 Sept 2012
DOIs	https://doi.org/10.1021/ml300132t
Publication status	Published - 13 Dec 2012
Externally published	Yes

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10.1021/ml300132tLicence: Unspecified

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@article{42a89000722641068afc8162c04fc279,

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.",

keywords = "C NMR, aziridinium, cancer, DNA, Imidazotetrazine, Temozolomide",

author = "Garelnabi, \{Elrashied A E\} and Dimitrios Pletsas and Li Li and Konstantinos Kiakos and Nazira Karodia and Hartley, \{John A.\} and Phillips, \{Roger M.\} and Wheelhouse, \{Richard T.\}",

year = "2012",

month = dec,

day = "13",

doi = "10.1021/ml300132t",

language = "English",

volume = "3",

pages = "965--968",

journal = "ACS Medicinal Chemistry Letters",

issn = "1948-5875",

publisher = "American Chemical Society",

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TY - JOUR

T1 - Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR

AU - Garelnabi, Elrashied A E

AU - Pletsas, Dimitrios

AU - Li, Li

AU - Kiakos, Konstantinos

AU - Karodia, Nazira

AU - Hartley, John A.

AU - Phillips, Roger M.

AU - Wheelhouse, Richard T.

PY - 2012/12/13

Y1 - 2012/12/13

N2 - 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.

AB - 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.

KW - C NMR

KW - aziridinium

KW - cancer

KW - DNA

KW - Imidazotetrazine

KW - Temozolomide

UR - https://www.scopus.com/pages/publications/84871241597

UR - http://pubs.acs.org/journal/amclct

U2 - 10.1021/ml300132t

DO - 10.1021/ml300132t

M3 - Article

AN - SCOPUS:84871241597

SN - 1948-5875

VL - 3

SP - 965

EP - 968

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 12

ER -

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

Abstract

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