Synthesis and cytotoxic activity of substituted 7-aryliminomethyl derivatives of camptothecin

Sabrina Dallavalle, Lucio Merlini, Gabriella Morini, Loana Musso, Sergio Penco, Giovanni Luca Beretta, Stella Tinelli, Franco Zunino

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)507-513
Number of pages7
JournalEuropean Journal of Medicinal Chemistry
Volume39
Issue number6
DOIs
Publication statusPublished - Jun 2004

Keywords

  • Antitumour
  • Camptothecin
  • Imines
  • Topoisomerase

ASJC Scopus subject areas

  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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