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

doi:10.1016/j.ejmech.2004.02.011

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

Fondazione IRCCS Istituto Nazionale dei Tumori

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	507-513
Number of pages	7
Journal	European Journal of Medicinal Chemistry
Volume	39
Issue number	6
DOIs	https://doi.org/10.1016/j.ejmech.2004.02.011
Publication status	Published - Jun 2004

Keywords

Antitumour
Camptothecin
Imines
Topoisomerase

ASJC Scopus subject areas

Molecular Medicine
Organic Chemistry
Drug Discovery
Pharmaceutical Science

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Synthesis and cytotoxic activity of substituted 7-aryliminomethyl derivatives of camptothecin. / Dallavalle, Sabrina; Merlini, Lucio; Morini, Gabriella; Musso, Loana; Penco, Sergio; Beretta, Giovanni Luca; Tinelli, Stella; Zunino, Franco.

In: European Journal of Medicinal Chemistry, Vol. 39, No. 6, 06.2004, p. 507-513.

Research output: Contribution to journal › Article › peer-review

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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.",

keywords = "Antitumour, Camptothecin, Imines, Topoisomerase",

author = "Sabrina Dallavalle and Lucio Merlini and Gabriella Morini and Loana Musso and Sergio Penco and Beretta, {Giovanni Luca} and Stella Tinelli and Franco Zunino",

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AU - Dallavalle, Sabrina

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AU - Morini, Gabriella

AU - Musso, Loana

AU - Penco, Sergio

AU - Beretta, Giovanni Luca

AU - Tinelli, Stella

AU - Zunino, Franco

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