Abstract
A series of imines derived from camptothecin-7-aldehyde (CPT-CHO) and aromatic amines were synthesised and tested for their cytotoxicity against tumour cell line H460, that expresses a high level of topoisomerase I. In general ortho-substituted compounds showed higher cytotoxic potency than the corresponding para-substituted imines. This effect was dependent on the nature of the substituent. Structure-activity relationships were studied by calculation of docking energy with a model of the ternary complex camptothecin-DNA- topoisomerase I. The ability of selected compounds to stimulate the topoisomerase I-mediated DNA cleavage and the persistence of the cleavable complex were consistent with the cytotoxic activity.
Original language | English |
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Pages (from-to) | 507-513 |
Number of pages | 7 |
Journal | European Journal of Medicinal Chemistry |
Volume | 39 |
Issue number | 6 |
DOIs | |
Publication status | Published - Jun 2004 |
Keywords
- Antitumour
- Camptothecin
- Imines
- Topoisomerase
ASJC Scopus subject areas
- Molecular Medicine
- Organic Chemistry
- Drug Discovery
- Pharmaceutical Science