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

100%

Bartulewicz D., Markowska A., Wolczynski S., Dabrowska M., Rozanski A.

Acta Biochimica Polonica

2000

tom 47

nr 1

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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Sequential fluorescent staining with CMA and DAPI for somatic chromosome identification in cucumber [Cucumis sativus L.]

80%

Plader W., Hoshi Y., Malepszy S.

Journal of Applied Genetics

1998

tom 39

nr 3

Each of the seven chromosomes in cucumber (Cucumis sativus L.) was identified using sequential staining with Chromomycin A₃ (CMA) and 4-6-diamidino-2-phenylindole (DAPI) as DNA base-specific fluorescent dyes. The present method using enzymatic digestion produced a high level of well-spread early-metaphase chromosome complements. After CMA and DAPI staining, reproducible fluorescence bands were obtained in mitotic prometaphase chromosomes. The CMA staining method made it possible to characterize whole chromosomes from prometaphase to mid-metaphase. Chromosome 1 had the largest and widest CMA-positive (CMA⁺) band from the proximal region to the interstitial region on the long arm in prometaphase. A large gap separating of the short arm from the long arm was always observed in chromosome 2 during prometaphase. The banding pattern of the short arm was similar to that of the long arm in chromosome 2. Chromosomes 1 and 2 in early metaphase had sharp and large CMA-positive and DAPI-negative (CMA⁺DAPI⁻) bands at the pericentromeric regions. In early metaphase, chromosome 3 was characterized by having a narrow CMA⁺DAPI⁻ band on the pericentromeric region of the short arm. Chromosomes 4 and 5 showed similar chromosome length and had a large CMA⁺ band at the distal region of the long arm. Chromosome 4 did not show any clear band in the short arm, while chromosome 5 showed a telomeric CMA⁺ band at the short arm and a clear CMA⁺DAPI⁻ band at the pericentromeric region. Chromosome 6 had a CMA⁺ band at the distal region and a weak CMA⁺ band at the proximal region in each of the arms. Chromosome 7 had an evident CMA⁺ band in the long arm and a CMA⁺ DAPI⁻ band in the pericentromeric region.

Inhibitory effects of pentamidine analogues on protein biosynthesis in vitro

80%

Bielawski K., Galicka A., Bielawska A., Sredzinska K.

Acta Biochimica Polonica

2000

tom 47

nr 1

Pentamidine despite its rather high toxicity, is currently in clinical use. For development of new drugs of this type it is important to know the mechanism of their action. Two new amidines (I and II) and 4',6-diamidino-2-phenylindole (DAPI) were found in preliminary experiments to inhibit protein synthesis in vitro in the cell-free rat liver system. The three compounds differed in the precise mode of action. The inhibitory effect of I on the activity of the eukaryotic elongation factor eEF-2 and ribosomes seems to suggest that the binding site of eEF-2 on the ribosome was blocked by this compound. eEF-2 has been identified as the primary target of II and eEF-1 as the primary target of DAPI in the system studied.

Ograniczanie wyników

2 Acta Biochimica Polonica

1 Journal of Applied Genetics

1 Bartulewicz D.

1 Bielawska A.

1 Bielawski K.

1 Dabrowska M.

1 Galicka A.

1 Hoshi Y.

1 Malepszy S.

1 Markowska A.

1 Plader W.

1 Rozanski A.

1 Sredzinska K.

1 Wolczynski S.

2 2000

1 1998

Wyniki wyszukiwania

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

Sequential fluorescent staining with CMA and DAPI for somatic chromosome identification in cucumber [Cucumis sativus L.]

Inhibitory effects of pentamidine analogues on protein biosynthesis in vitro