DNA interaction and topoisomerase II inhibition by the antitumor agent 3'-(9-acridinylamino)-5'-hydroxymethylaniline and derivatives Journal Article
| Authors: | Scarborough, A.; Su, T. L.; Leteutre, F. F.; Pommier, Y.; Chou, T. C. |
| Article Title: | DNA interaction and topoisomerase II inhibition by the antitumor agent 3'-(9-acridinylamino)-5'-hydroxymethylaniline and derivatives |
| Abstract: | Cleavage and cytotoxicity assays have been used to show that 3'-(9-acridinylamino)-5'-hydroxymethylaniline (AHMA) is a potent antileukemic agent that inhibits topoisomerase II-mediated relaxation of supercoiled DNA and promotes the topoisomerase II-mediated cleavage of DNA at a subset of the cleavage sites of 4'-(9-acridinylamino)-methanesulfon-m-anisidide (m-AMSA). Equilibrium binding data show a larger binding constant for the more cytotoxic derivatives for binding to poly(dA-dT)2 as compared to poly(dG-dC)2, but greater cooperativity for binding to poly(dG-dC)2 and a steric barrier to binding caused by the size of the 5'-hydroxymethyl substituent. Circular dichroism shows a more intercalated binding geometry on poly(dG-dC)2 for 1'-substituted derivatives when compared to AHMA and derivatives with a free 1'-amino group, which is absent with poly(dA-dT)2 and calf thymus DNA and is indicative of specific interactions with GC-rich areas in natural DNA for AHMA and derivatives with free 1'-amino groups which may stabilize the drug-DNA complex. |
| Keywords: | controlled study; unclassified drug; antineoplastic agent; antineoplastic activity; in vitro study; 3 (9 acridinylamino) 5 hydroxymethylaniline; amsacrine; dna topoisomerase (atp hydrolysing); dna binding; dna cleavage; circular dichroism; aniline derivative; priority journal; article |
| Journal Title: | Bioorganic Chemistry |
| Volume: | 24 |
| Issue: | 3 |
| ISSN: | 0045-2068 |
| Publisher: | Academic Press Inc., Elsevier Science |
| Date Published: | 1996-09-01 |
| Start Page: | 229 |
| End Page: | 241 |
| Language: | English |
| DOI: | 10.1006/bioo.1996.0021 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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