Abstract
The interaction of AMSA with nucleic acids was studied by several techniques. Melting temperature and CD studies equally suggest that AMSA-binding is interfering with the secondary structure of DNA. An overlap by two mechanism of binding seems to exist. Based on the CD measurements at low drug concentration intercalation is the most likely way of binding. At higher drug concentration stacking interaction predominates leading to cooperativity and formation of oriented sheets of aromatic ring-systems as reflected in the optical activity induced in the metachromatic band of the achiral drug. No base-pair specificity could be confirmed; however, a high affinity of AMSA to poly(A) chains was demonstrated. The CD measurements did not indicate any significant interaction with RNA. The selectivity of the AMSA-DNA interaction can be regarded as an important argument in favour of the role of this interaction in the anti-tumour effect of the drug.
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Selected References
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- Cain B. F., Atwell G. J., Denny W. A. Potential antitumor agents. 16.4'-(Acridin-9-ylamino)methanesulfonanilides. J Med Chem. 1975 Nov;18(11):1110–1117. doi: 10.1021/jm00245a013. [DOI] [PubMed] [Google Scholar]
- Cain B. F., Seelye R. N., Atwell G. J. Potential antitumor agents. 14. Acridylmethanesulfonanilides. J Med Chem. 1974 Sep;17(9):922–930. doi: 10.1021/jm00255a003. [DOI] [PubMed] [Google Scholar]
- Deaven L. L., Oka M. S., Tobey R. A. Cell-cycle-specific chromosome damage following treatment of cultured Chinese hamster cells with 4'-[(9-acridinyl)-amino]methanesulphon-m-anisidide-HCl. J Natl Cancer Inst. 1978 May;60(5):1155–1161. [PubMed] [Google Scholar]
- Gormley P. E., Sethi V. S., Cysyk R. L. Interaction of 4'-(9-acridinylamino)methanesulfon-m-anisidide with DNA and inhibition of oncornavirus reverse transcriptase and cellular nucleic acid polymerases. Cancer Res. 1978 May;38(5):1300–1306. [PubMed] [Google Scholar]
- Löber G., Achtert G. On the complex formation of acridine dyes with DNA. VII. Dependence of the binding on the dye structure. Biopolymers. 1969;8(5):595–608. doi: 10.1002/bip.1969.360080504. [DOI] [PubMed] [Google Scholar]
- Papaphilis A. D., Shaw Y. H. Interaction of acridines and tetrahydroacridines with DNA at low DNA/dye ratios. Biochim Biophys Acta. 1977 May 17;476(2):122–130. doi: 10.1016/0005-2787(77)90089-2. [DOI] [PubMed] [Google Scholar]
- Sachdev G. P., Brownstein A. D., Fruton J. S. Interaction of 9-peptidylaminoacridines with proteins and nucleic acids. J Biol Chem. 1974 Jan 25;249(2):420–427. [PubMed] [Google Scholar]
- Sinha B. K., Chignell C. F. Interaction of antitumor drugs with human erythrocyte ghost membranes and mastocytoma P815: a spin label study. Biochem Biophys Res Commun. 1979 Feb 28;86(4):1051–1057. doi: 10.1016/0006-291x(79)90223-7. [DOI] [PubMed] [Google Scholar]
- Tobey R. A., Deaven L. L., Oka M. S. Kinetic response of cultured Chinese hamster cells to treatment with 4'-[(9-acridinyl)-amino]methanesulphon-m-anisidide-HCl. J Natl Cancer Inst. 1978 May;60(5):1147–1153. doi: 10.1093/jnci/60.5.1147. [DOI] [PubMed] [Google Scholar]
- Van Echo D. A., Chiuten D. F., Gormley P. E., Lichtenfeld J. L., Scoltock M., Wiernik P. H. Phase I clinical and pharmacological study of 4'-(9-acridinylamino)-methanesulfon-m-anisidide using an intermittent biweekly schedule. Cancer Res. 1979 Oct;39(10):3881–3884. [PubMed] [Google Scholar]
- Waring M. J. DNA-binding characteristics of acridinylmethanesulphonanilide drugs: comparison with antitumour properties. Eur J Cancer. 1976 Dec;12(12):995–1001. doi: 10.1016/0014-2964(76)90066-9. [DOI] [PubMed] [Google Scholar]