Synthesis and cytotoxic evaluation of combretafurazans

Gian Cesare Tron; Francesca Pagliai; Erika Del Grosso; Armando A. Genazzani; Giovanni Sorba

doi:10.1021/jm049096o

Synthesis and cytotoxic evaluation of combretafurazans

Gian Cesare Tron, Francesca Pagliai, Erika Del Grosso, Armando A. Genazzani, Giovanni Sorba

Department of Pharmaceutical Sciences

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

Abstract

Combretastatin A-4 is an antitumoral and antitubulin agent that is active only in its cis configuration. In the present manuscript, we have synthesized cis-locked combretastatins embodying a furazan ring (combretafurazans). To achieve this, we have developed a new strategy that exploits the dehydration of vicinal dioximes using the Mitsunobu reaction. Among the advantages of following such a strategy are the mild conditions used for the construction of the diarylfurazan derivatives, allowing for the presence of highly functionalized substrates and deactivated aromatic rings. Combretafurazans are more potent in vitro cytotoxic compounds compared to combretastatins in neuroblastoma cells, yet maintaining similar structure-activity relationship and pharmacodynamic profiles.

Original language	English
Pages (from-to)	3260-3268
Number of pages	9
Journal	Journal of Medicinal Chemistry
Volume	48
Issue number	9
DOIs	https://doi.org/10.1021/jm049096o
Publication status	Published - 5 May 2005

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abstract = "Combretastatin A-4 is an antitumoral and antitubulin agent that is active only in its cis configuration. In the present manuscript, we have synthesized cis-locked combretastatins embodying a furazan ring (combretafurazans). To achieve this, we have developed a new strategy that exploits the dehydration of vicinal dioximes using the Mitsunobu reaction. Among the advantages of following such a strategy are the mild conditions used for the construction of the diarylfurazan derivatives, allowing for the presence of highly functionalized substrates and deactivated aromatic rings. Combretafurazans are more potent in vitro cytotoxic compounds compared to combretastatins in neuroblastoma cells, yet maintaining similar structure-activity relationship and pharmacodynamic profiles.",

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T1 - Synthesis and cytotoxic evaluation of combretafurazans

AU - Tron, Gian Cesare

AU - Pagliai, Francesca

AU - Del Grosso, Erika

AU - Genazzani, Armando A.

AU - Sorba, Giovanni

PY - 2005/5/5

Y1 - 2005/5/5

N2 - Combretastatin A-4 is an antitumoral and antitubulin agent that is active only in its cis configuration. In the present manuscript, we have synthesized cis-locked combretastatins embodying a furazan ring (combretafurazans). To achieve this, we have developed a new strategy that exploits the dehydration of vicinal dioximes using the Mitsunobu reaction. Among the advantages of following such a strategy are the mild conditions used for the construction of the diarylfurazan derivatives, allowing for the presence of highly functionalized substrates and deactivated aromatic rings. Combretafurazans are more potent in vitro cytotoxic compounds compared to combretastatins in neuroblastoma cells, yet maintaining similar structure-activity relationship and pharmacodynamic profiles.

AB - Combretastatin A-4 is an antitumoral and antitubulin agent that is active only in its cis configuration. In the present manuscript, we have synthesized cis-locked combretastatins embodying a furazan ring (combretafurazans). To achieve this, we have developed a new strategy that exploits the dehydration of vicinal dioximes using the Mitsunobu reaction. Among the advantages of following such a strategy are the mild conditions used for the construction of the diarylfurazan derivatives, allowing for the presence of highly functionalized substrates and deactivated aromatic rings. Combretafurazans are more potent in vitro cytotoxic compounds compared to combretastatins in neuroblastoma cells, yet maintaining similar structure-activity relationship and pharmacodynamic profiles.

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JO - Journal of Medicinal Chemistry

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Synthesis and cytotoxic evaluation of combretafurazans

Abstract

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