Molecular modelling, synthesis and antitumour activity of carbocyclic analogues of netropsin and distamycin -: new carriers of alkylating elements

被引：19
作者：
Bartulewicz, D
Markowska, A
Wolczynski, S
Dabrowska, M
Rózanski, A
机构：
[1] Med Acad Bialystok, Dept Organ Chem, Bialystok, Poland
[2] Med Acad Bialystok, Dept Gynaecol Endocrinol, Bialystok, Poland
[3] Med Acad Bialystok, Dept Diagnost Haematol, Bialystok, Poland
来源：
ACTA BIOCHIMICA POLONICA | 2000年 / 47卷 / 01期
关键词：
carbocyclic analogues of distamycin and netropsin; lexitropsin; molecular modelling;
D O I：
10.18388/abp.2000_4059
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 series of netropsin and distamycin analogues was synthesised and investigated by molecular modelling. The lowest-energy conformations of four carbocyclic lexitropsins, potential carriers of alkylating elements, were obtained using the HyperChem 4.0 program, and compared with the DNA-lexitropsin crystal structures from the Brookhaven National Laboratory Protein Data Bank. A method for synthesis of carbocyclic lexitropsins was elaborated, with the use of a nitro group or azobenzene as precursors for the aromatic amino group. The influence of methoxy group in ortho position with respect to amide groups on the activity of the new compounds was investigated. All of the compounds tested showed high antitumour activity in the standard cell line of mammalian tumour MCF-7.
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页码：23 / 35
页数：13
相关论文
共 38 条
  • [1] DESIGN AND SYNTHESIS OF ANTHRACYCLINE AND DISTAMYCIN DERIVATIVES AS NEW, SEQUENCE-SPECIFIC, DNA-BINDING PHARMACOLOGICAL AGENTS
    ARCAMONE, F
    [J]. GENE, 1994, 149 (01) : 57 - 61
  • [2] *AUT INC, HYP VERS 3 0
  • [3] Sequence-specific DNA minor groove binders. Design and synthesis of netropsin and distamycin analogues
    Bailly, C
    Chaires, JB
    [J]. BIOCONJUGATE CHEMISTRY, 1998, 9 (05) : 513 - 538
  • [4] Synthetic analogues of netropsin and distamycin - synthesis of a new pyridine and carbocyclic analogues of the pyrrolecarboxamide antitumour antibiotics
    Bartulewicz, D
    Bielawski, K
    Markowska, A
    Zwierz, K
    Puckowska, A
    Rozanski, A
    [J]. ACTA BIOCHIMICA POLONICA, 1998, 45 (01) : 41 - 57
  • [5] Bartulewicz D, 1995, Rocz Akad Med Bialymst, V40, P364
  • [6] Synthesis and in vitro efficacy of transferrin conjugates of the anticancer drug chlorambucil
    Beyer, U
    Roth, T
    Schumacher, P
    Maier, G
    Unold, A
    Frahm, AW
    Fiebig, HH
    Unger, C
    Kratz, F
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (15) : 2701 - 2708
  • [7] STRUCTURE-ACTIVITY-RELATIONSHIPS OF PYRROLE AMIDINE ANTI-VIRAL ANTIBIOTICS .1. MODIFICATIONS OF THE ALKYLAMIDINE SIDE-CHAIN
    BIALER, M
    YAGEN, B
    MECHOULAM, R
    BECKER, Y
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1979, 22 (11) : 1296 - 1301
  • [8] Bielawski K, 1996, Rocz Akad Med Bialymst, V41, P293
  • [9] Bielawski K, 1995, Rocz Akad Med Bialymst, V40, P352
  • [10] Backbone and benzoyl mustard carrying moiety modifies DNA interactions of distamycin analogues
    Ciucci, A
    Manzini, S
    Lombardi, P
    Arcamone, F
    [J]. NUCLEIC ACIDS RESEARCH, 1996, 24 (02) : 311 - 315
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