The anti-cancer, anti-inflammatory and tuberculostatic activities of a series of 6,7-substituted-5,8-quinolinequinones

被引：72

作者：

Mulchin, Benjamin J. ^{[2
]}

Newton, Christopher G. ^{[1
,2
]}

Baty, James W. ^{[2
]}

Grasso, Carole H. ^{[2
]}

Martin, William John ^{[2
]}

Walton, Michaela C. ^{[2
]}

Dangerfield, Emma M. ^{[1
,2
]}

Plunkett, Catherine H. ^{[1
,2
]}

Berridge, Michael V. ^{[2
]}

Harper, Jacquie L. ^{[2
]}

Timmer, Mattie S. M. ^{[1
]}

Stocker, Bridget L. ^{[2
]}

机构：

[1] Victoria Univ Wellington, Sch Chem & Phys Sci, Wellington, New Zealand

[2] Malaghan Inst Med Res, Wellington, New Zealand

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 09期

关键词：

Quinolinequinone; Cancer; Tuberculosis; Inflammation; Synthesis; NEUTROPHIL RESPIRATORY BURST; MEMBRANE ELECTRON-TRANSPORT; ANTITUMOR ANTIBIOTICS; TETRAZOLIUM SALT; STREPTONIGRIN; INHIBITORS; QUINONES; ASSAY; INFLAMMATION; REDUCTION;

D O I：

10.1016/j.bmc.2010.03.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A variety of 6,7-substituted-5,8-quinolinequinones were synthesised and assessed for their anti-tumour and anti-inflammatory activities, and their ability to inhibit the growth of Mycobacterium bovis BCG. In particular, the introduction of a sulfur group at the 7-position of the quinolinequinone led to the discovery of two compounds, 6-methylamino-7-methylsulfanyl-5,8-quinolinequinone (10a) and 6-amino-7-methylsulfonyl-5,8-quinolinequinone ( 12), that exhibited selectivity for leukemic cells over T-cells, a highly desirable property for an anti-cancer drug. A number of anti-inflammatory ( AI) compounds were also identified, with 6,7-bis-methylsulfanyl-5,8-quinolinequinone (18a) exhibiting the highest AI activity (0.11 mu M), while 6,7-dichloro-5,8-quinolinequinone (7a), 6,7-dichloro-2-methyl-5,8-quinolinequinone (7b), and 6,7-bis-phenylsulfanyl-quinoline-5,8-diol ( 19) also exhibited good AI activity and specificity. Several quinolinequinone TB-drug candidates were identified. Of these, 6-amino-7-chloro-5,8-quinolinequinone ( 11) and 6-amino-7-methanesulfinyl-5,8-quinolinequinone ( 14), exhibited low MICs (1.56-3.13 mu g/mL) for the 100% growth inhibition of M. Bovis BCG. Some general trends pertaining to the functional group substitution of the quinolinequinone core and biological activity were also identified. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：3238 / 3251

页数：14

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