Synthesis and cytotoxic activity of a new series of topoisomerase I inhibitors

Sabrina Dallavalle; Sonia Gattinoni; Stefania Mazzini; Leonardo Scaglioni; Lucio Merlini; Stella Tinelli; Giovanni L. Beretta; Franco Zunino

doi:10.1016/j.bmcl.2007.12.055

Synthesis and cytotoxic activity of a new series of topoisomerase I inhibitors

Sabrina Dallavalle, Sonia Gattinoni, Stefania Mazzini, Leonardo Scaglioni, Lucio Merlini, Stella Tinelli, Giovanni L. Beretta, Franco Zunino

Fondazione IRCCS Istituto Nazionale dei Tumori

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

Abstract

A series of structurally simple analogues of natural topopyrone C were synthesized and tested for cytotoxic and topoisomerase I inhibitory activities. The removal of the hydroxyl groups at the 5 and 9 positions resulted in an increased cytotoxic potency and ability to stabilize topoisomerase-mediated cleavage. In addition, the results suggest that some structural features, such as the pyrone ring and a polar group in position 11, are fundamental for topoisomerase I inhibitory effect. These structural requirements are also consistent with the cytotoxic activity.

Original language	English
Pages (from-to)	1484-1489
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	4
DOIs	https://doi.org/10.1016/j.bmcl.2007.12.055
Publication status	Published - Feb 15 2008

Keywords

Antitumor
Cytotoxic activity
Topoisomerase I
Topopyrones

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Organic Chemistry
Drug Discovery
Pharmaceutical Science

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10.1016/j.bmcl.2007.12.055

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Synthesis and cytotoxic activity of a new series of topoisomerase I inhibitors. / Dallavalle, Sabrina; Gattinoni, Sonia; Mazzini, Stefania; Scaglioni, Leonardo; Merlini, Lucio; Tinelli, Stella; Beretta, Giovanni L.; Zunino, Franco.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 18, No. 4, 15.02.2008, p. 1484-1489.

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

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abstract = "A series of structurally simple analogues of natural topopyrone C were synthesized and tested for cytotoxic and topoisomerase I inhibitory activities. The removal of the hydroxyl groups at the 5 and 9 positions resulted in an increased cytotoxic potency and ability to stabilize topoisomerase-mediated cleavage. In addition, the results suggest that some structural features, such as the pyrone ring and a polar group in position 11, are fundamental for topoisomerase I inhibitory effect. These structural requirements are also consistent with the cytotoxic activity.",

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AU - Merlini, Lucio

AU - Tinelli, Stella

AU - Beretta, Giovanni L.

AU - Zunino, Franco

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N2 - A series of structurally simple analogues of natural topopyrone C were synthesized and tested for cytotoxic and topoisomerase I inhibitory activities. The removal of the hydroxyl groups at the 5 and 9 positions resulted in an increased cytotoxic potency and ability to stabilize topoisomerase-mediated cleavage. In addition, the results suggest that some structural features, such as the pyrone ring and a polar group in position 11, are fundamental for topoisomerase I inhibitory effect. These structural requirements are also consistent with the cytotoxic activity.

AB - A series of structurally simple analogues of natural topopyrone C were synthesized and tested for cytotoxic and topoisomerase I inhibitory activities. The removal of the hydroxyl groups at the 5 and 9 positions resulted in an increased cytotoxic potency and ability to stabilize topoisomerase-mediated cleavage. In addition, the results suggest that some structural features, such as the pyrone ring and a polar group in position 11, are fundamental for topoisomerase I inhibitory effect. These structural requirements are also consistent with the cytotoxic activity.

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KW - Cytotoxic activity

KW - Topoisomerase I

KW - Topopyrones

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Synthesis and cytotoxic activity of a new series of topoisomerase I inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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