Biological evaluation of bishydroxymethyl-substituted cage dimeric 1,4-dihydropyridines as a novel class of P-glycoprotein modulating agents in cancer cells

被引：30

作者：

Richter, M

Molnár, J

Hilgeroth, A

机构：

[1] Univ Halle Wittenberg, Inst Pharmaceut Chem, D-06120 Halle, Germany

[2] Univ Szeged, Fac Med, Dept Med Microbiol, H-6720 Szeged, Hungary

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 09期

关键词：

D O I：

10.1021/jm058046w

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of N-substituted cage dimeric 1,4-dihydropyridines 3a-e was evaluated as inhibitors of membrane efflux pump P-glycoprotein (P-gp) in multidrug resistant (mdr) cancer cells. Structure-activity relationships (SAR) and cytotoxic properties are discussed. Effective concentrations for overcoming mdr have been demonstrated in competition studies with the P-gp substrate epirubicin.

引用

收藏

页码：2838 / 2840

页数：3

相关论文

共 14 条

[1] A STUDY OF THE PRIMARY ACID REACTION ON MODEL COMPOUNDS OF REDUCED DIPHOSPHOPYRIDINE NUCLEOTIDE [J].

ANDERSON, AG ;

BERKELHAMMER, G .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1958, 80 (04) :992-999

[2] Designing multidrug-resistance modulators circumventing the reverse pH gradient in tumours [J].

Castaing, M ;

Loiseau, A ;

Dani, M .

JOURNAL OF PHARMACY AND PHARMACOLOGY, 2001, 53 (07) :1021-1028

[3]

Dassow H, 2000, INT J CLIN PHARM TH, V38, P209

[4] BIOCHEMISTRY OF MULTIDRUG-RESISTANCE MEDIATED BY THE MULTIDRUG TRANSPORTER [J].

GOTTESMAN, MM ;

PASTAN, I .

ANNUAL REVIEW OF BIOCHEMISTRY, 1993, 62 :385-427

[5] Lipids as a target for drugs modulating multidrug resistance of cancer cells [J].

Hendrich, AB ;

Michalak, K .

CURRENT DRUG TARGETS, 2003, 4 (01) :23-30

[6] Synthesis and biological evaluation of the first N-alkyl cage dimeric 4-aryl-1,4-dihydropyridines as novel nonpeptidic HIV-1 protease inhibitors [J].

Hilgeroth, A ;

Wiese, M ;

Billich, A .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (22) :4729-4732

[7] First rotameric anti dimers and 3,9-diazatetraasteranes from unsymmetrically substituted N-acyl- and N-acyloxy-4-aryl-1,4dihydropyridines [J].

Hilgeroth, A ;

Heinemann, FW ;

Baumeister, U .

HETEROCYCLES, 2002, 57 (06) :1003-1016

[8] MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models [J].

Mahon, FX ;

Belloc, F ;

Lagarde, V ;

Chollet, C ;

Moreau-Gaudry, F ;

Reiffers, J ;

Goldman, JM ;

Melo, JV .

BLOOD, 2003, 101 (06) :2368-2373

[9] Reduced effect of gemtuzumab ozogamicin (CMA-676) on P-glycoprotein and/or CD34-positive leukemia cells and its restoration by multidrug resistance modifiers [J].

Matsui, H ;

Takeshita, A ;

Naito, K ;

Shinjo, K ;

Shigeno, K ;

Maekawa, M ;

Yamakawa, Y ;

Tanimoto, M ;

Kobayashi, M ;

Ohnishi, K ;

Ohno, R .

LEUKEMIA, 2002, 16 (05) :813-819

[10]

Pauli-Magnus C, 2000, J PHARMACOL EXP THER, V293, P376