Naphthalene combretastatin analogues:: Synthesis, cytotoxicity and antitubulin activity

被引：64

作者：

Medarde, M ^{[1
]}

Maya, ABS ^{[1
]}

Pérez-Melero, C ^{[1
]}

机构：

[1] Univ Salamanca, Fac Farm, Lab Quim Organ & Farmaceut, E-37007 Salamanca, Spain

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2004年 / 19卷 / 06期

关键词：

combretastatin analogues; SAR; naphthalene derivatives; quinoline derivatives; cytotoxicity; tubulin polymerization inhibition;

D O I：

10.1080/14756360412331280473

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：

Synthesis and evaluation of new combretastatin analogues with varied modifications on the bridge and the aromatic rings, have shown that the 2-naphthyl moiety is a good surrogate for the 3-hydroxy-4-methoxyphenyl (B-ring) of combretastatin A-4. Other bicyclic systems, such as 6(7)-quinolyl and 5-indolyl, can replace the B-ring, but they produce less potent analogues in the cytotoxicity and tubulin polymerization inhibition assays. Other modifications are detrimentral for the potency of the studied analogues. The 2-naphthyl combretastatin 53 and the related 6-quinolyl combretastatin 106 analogues are the most potent among the derivatives of this type, whereas 92 and 95 are the most potent among the naphthalene derivatives with a heterocycle in the bridge. Previous and new results in this family of combretastatin analogues are discussed.

引用

页码：521 / 540

页数：20

共 62 条

[1]

BAI R, 1990, J BIOL CHEM, V265, P17141

[2] Synthesis of water-soluble prodrugs of the cytotoxic agent combretastatin A4. [J].

Bedford, SB ;

Quarterman, CP ;

Rathbone, DL ;

Slack, JA ;

Griffin, RJ ;

Stevens, MFG .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1996, 6 (02) :157-160

[3]

BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3

[4] Comparative molecular field analysis of colchicine inhibition and tubulin polymerization for combretastatins binding to the colchicine binding site on β-tubulin [J].

Brown, ML ;

Rieger, JM ;

Macdonald, TL .

BIOORGANIC & MEDICINAL CHEMISTRY, 2000, 8 (06) :1433-1441

[5] SYNTHESIS OF WATER-SOLUBLE SUGAR-DERIVATIVES OF COMBRETASTATIN A-4 [J].

BROWN, RT ;

FOX, BW ;

HADFIELD, JA ;

MCGOWN, AT ;

MAYALARP, SP ;

PETTIT, GR ;

WOODS, JA .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1995, (05) :577-581

[6] Preparation of new anti-tubulin ligands through a dual-mode, addition-elimination reaction to a bromo-substituted α,β-unsaturated sulfoxide [J].

Chen, Z ;

Mocharla, VP ;

Farmer, JM ;

Pettit, GR ;

Hamel, E ;

Pinney, KG .

JOURNAL OF ORGANIC CHEMISTRY, 2000, 65 (25) :8811-8815

[7]

Cooper G.M., 1993, CANC BOOK

[8] SYNTHESIS AND EVALUATION OF STILBENE AND DIHYDROSTILBENE DERIVATIVES AS POTENTIAL ANTICANCER AGENTS THAT INHIBIT TUBULIN POLYMERIZATION [J].

CUSHMAN, M ;

NAGARATHNAM, D ;

GOPAL, D ;

CHAKRABORTI, AK ;

LIN, CM ;

HAMEL, E .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (08) :2579-2588

[9] SYNTHESIS AND EVALUATION OF A SERIES OF BENZYLANILINE HYDROCHLORIDES AS POTENTIAL CYTOTOXIC AND ANTIMITOTIC AGENTS ACTING BY INHIBITION OF TUBULIN POLYMERIZATION [J].

CUSHMAN, M ;

HE, HM ;

LIN, CM ;

HAMEL, E .

JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (19) :2817-2821

[10] SYNTHESIS AND EVALUATION OF ANALOGS OF (Z)-1-(4-METHOXYPHENYL)-2-(3,4,5-TRIMETHOXYPHENYL)ETHENE AS POTENTIAL CYTOTOXIC AND ANTIMITOTIC AGENTS [J].

CUSHMAN, M ;

NAGARATHNAM, D ;

GOPAL, D ;

HE, HM ;

LIN, CM ;

HAMEL, E .

JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (12) :2293-2306

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