4′-Alkoxyl substitution enhancing the anti-mitotic effect of 5-(3′,4′,5′-substituted)anilino-4-hydroxy-8-nitroquinazolines as a novel class of anti-microtubule agents

被引：24

作者：

Jin, Yi

Zhou, Zu-Yu

Tian, Wei

Yu, Qiang

Long, Ya-Qiu

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China

[2] Shenyang Pharmaceutb Univ, Sch Pharmaceut Engn, Liaoning 110016, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 22期

关键词：

quinazoline; mitosis inhibitor; tubulin polymerization; anti-microtubule agent; alkoxyl substitution; aniline; antiproliferative effect; cell cycle; tumor cells;

D O I：

10.1016/j.bmcl.2006.08.058

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Mitosis inhibitors are powerful anticancer drugs. Based on a novel anti-microtubule agent of 5-(4'-methoxy)anilino-4-hydroxy-8-nitroquinazoline, a series of 5-(3',4',5'-substituted)anilino-4-hydroxy-8- nitroquinazolines were designed and synthesized to investigate the effect of the substitution on the inhibitory activity against mitotic progression of tumor cells. The large alkoxyl substitution on the 4'-position of 5-anilino ring is beneficial for the potency. The 5-(3',4,5'-trimethoxy)anilino-8-nitroquinazoline (1h) displays an overwhelming activity in arresting the cells at the G2/M phase, providing a promising new template for further development of potent microtubule-targeted anti-mitotic drugs. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：5864 / 5869

页数：6

共 21 条

[1]

[Anonymous], CANC PRINCIPLES PRAC

[2]

[Anonymous], 1983, J IMMUNOL METH

[3] 5-Substituted 4-anilinoquinazolines as potent, selective and orally active inhibitors of erbB2 receptor tyrosine kinase [J].

Ballard, P ;

Bradbury, RH ;

Hennequin, LFA ;

Hickinson, DM ;

Johnson, PD ;

Kettle, JG ;

Klinowska, T ;

Morgentin, R ;

Ogilvie, DJ ;

Olivier, A .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (19) :4226-4229

[4] 2-Aminoquinazoline inhibitors of cyclin-dependent kinases [J].

Bathini, Y ;

Singh, I ;

Harvey, PJ ;

Keller, PR ;

Singh, R ;

Micetich, RG ;

Fry, DW ;

Dobrusin, EM ;

Toogood, PL .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (17) :3881-3885

[5]

Ciardiello F, 2001, CLIN CANCER RES, V7, P2958

[6] Synthesis of quinazolinones and quinazolines [J].

Connolly, DJ ;

Cusack, D ;

O'Sullivan, TP ;

Guiry, PJ .

TETRAHEDRON, 2005, 61 (43) :10153-10202

[7] Mechanisms of action of and resistance to antitubulin agents: Microtubule dynamics, drug transport, and cell death [J].

Dumontet, C ;

Sikic, BI .

JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (03) :1061-1070

[8] Mechanisms of cancer drug resistance [J].

Gottesman, MM .

ANNUAL REVIEW OF MEDICINE, 2002, 53 :615-627

[9] Synthesis and characterization of 3-arylquinazolinone and 3-arylquinazolinethione derivatives as selective estrogen receptor beta modulators [J].

Güngör, T ;

Chen, Y ;

Golla, R ;

Ma, ZP ;

Corte, JR ;

Northrop, JP ;

Bin, B ;

Dickson, JK ;

Stouch, T ;

Zhou, R ;

Johnson, SE ;

Seethala, R ;

Feyen, JHM .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (08) :2440-2455

[10] Synthesis and antitumor evaluation of novel 5-substituted-4-hydroxy-8-nitroquinazolines as EGFR signaling-targeted inhibitors [J].

Jin, Y ;

Li, HY ;

Lin, LP ;

Tan, JZ ;

Ding, J ;

Luo, XM ;

Long, YQ .

BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (19) :5613-5622

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