Indirect and Direct Detection of the 4-(Benzothiazol-2-yl)phenylnitrenium Ion from a Putative Metabolite of a Model Anti-Tumor Drug

被引：23

作者：

Chakraborty, Mrinal ^{[1
]}

Jin, Kyoung Joo ^{[1
]}

Brewer, Samuel C., III ^{[1
]}

Peng, Huo-Lei ^{[2
]}

Platz, Matthew S. ^{[2
]}

Novak, Michael ^{[1
]}

机构：

[1] Miami Univ, Dept Chem & Biochem, Oxford, OH 45056 USA

[2] Ohio State Univ, Dept Chem, Columbus, OH 43210 USA

来源：

ORGANIC LETTERS | 2009年 / 11卷 / 21期

基金：

美国国家科学基金会;

关键词：

BREAST-CANCER CELLS; 1-PHENYLETHYL DERIVATIVES; IN-VITRO; 2-(4-AMINOPHENYL)BENZOTHIAZOLES; BENZOTHIAZOLES; WATER; ACID; DECOMPOSITION; SELECTIVITY; GENERATION;

D O I：

10.1021/ol901959z

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

2-(4-Aminophenyl)benzothiazoles related to 1 are potentially important pharmaceuticals. Metabolism apparently involves oxidation and esterification to 3. In water, hydrolysis and photolysis of 3 generates the nitrenium ion 4 that can be detected indirectly by N-3(-). trapping and directly by UV-vis spectroscopy following laser flash photolysis. The transient, with lambda(max) 570 nm, and a lifetime of 530 ns, reacts with N-3(-) at a diffusion-controlled rate and generates the quinol 6 by reaction with water.

引用

页码：4862 / 4865

页数：4

共 22 条

[1] The development of the antitumour benzothiazole prodrug, Phortress, as a clinical candidate [J].

Bradshaw, TD ;

Westwell, AD .

CURRENT MEDICINAL CHEMISTRY, 2004, 11 (08) :1009-1021

[2] 2-(4-aminophenyl)benzothiazoles: novel agents with selective profiles of in vitro anti-tumour activity [J].

Bradshaw, TD ;

Wrigley, S ;

Shi, DF ;

Schultz, RJ ;

Paull, KD ;

Stevens, MFG .

BRITISH JOURNAL OF CANCER, 1998, 77 (05) :745-752

[3] Anti-tumor drug candidate 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole induces single-strand breaks and DNA-protein cross-links in sensitive MCF-7 breast cancer cells [J].

Brantley, E ;

Antony, S ;

Kohlhagen, G ;

Meng, LH ;

Agama, K ;

Stinson, SF ;

Sausville, EA ;

Pommier, Y .

CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2006, 58 (01) :62-72

[4]

Chua MS, 2000, CANCER RES, V60, P5196

[5] DFT-investigation of nitrenium ions derived from metabolism of antitumor 2-(4-aminophenyl)benzothiazoles [J].

Hilal, R ;

Abdel Khalek, AA ;

Elroby, SAK .

JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM, 2005, 731 (1-3) :115-121

[6] Antitumor benzothiazoles. 16. Synthesis and pharmaceutical properties of antitumor 2-(4-aminophenyl)benzothiazole amino acid prodrugs [J].

Hutchinson, I ;

Jennings, SA ;

Vishnuvajjala, BR ;

Westwell, AD ;

Stevens, MFG .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (03) :744-747

[7] Synthesis and characterization of the food-derived carcinogens 2-(hydroxylamino)-α-carboline and 2-(hydroxylamino)-3-methyl-α-carboline [J].

Kazerani, S ;

Novak, M .

JOURNAL OF ORGANIC CHEMISTRY, 1998, 63 (03) :895-897

[8] ELECTRON-DEFICIENT STRONG BASES - GENERATION OF THE 4-BIPHENYLYLNITRENIUM AND 2-FLUORENYLNITRENIUM IONS BY NITRENE PROTONATION IN WATER [J].

MCCLELLAND, RA ;

DAVIDSE, PA ;

HADZIALIC, G .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (14) :4173-4174

[9] Generation and trapping of the 4-biphenylyloxenium ion by water and azide: Comparisons with the 4-biphenylyinitrenium ion [J].

Novak, M ;

Glover, SA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (25) :7748-7749

[10] REACTIVITY AND SELECTIVITY OF NITRENIUM IONS DERIVED FROM ESTER DERIVATIVES OF CARCINOGENIC N-(4-BIPHENYLYL)HYDROXYLAMINE AND THE CORRESPONDING HYDROXAMIC ACID [J].

NOVAK, M ;

KAHLEY, MJ ;

EIGER, E ;

HELMICK, JS ;

PETERS, HE .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (21) :9453-9460

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