Introduction: Our research group has directed its attention to the identification of structurally new vascular disrupting agents (VDAs) which are water soluble or may be converted into water soluble derivatives, possess vascular disrupting activity, and show antitumor activity at non- toxic doses. We prepared 1,5- and 1,2-diaryl-1H-imidazoles of general formula 1 and 2, respectively, which can be considered as cis-locked analogues of combretastatin A-4 (CA-4), a natural tubulin-binding VDA. We became interested in the imidazole core since its basic nitrogen atom may lead to compounds which can easily be formulated as water-soluble salts. Moreover, since the 3,4,5-trimethoxyphenyl substituted A ring of the CA-4 seems to be essential for the activity of this natural product, we maintained this moiety in compounds 1 and 2 and evaluated the effect due to the replacement of the B-ring of CA-4 with a variety of aryl substituents. Material and Methods: Imidazoles 1 and 2 were prepared using the innovative synthetic protocols we recently developed. The vascular disrupting activity of some selected compounds was evaluated in vitro on HUVEC, and in vivo on experimental tumors.

Imidazole derivatives with vascular disrupting activity

BELLINA, FABIO;
2006-01-01

Abstract

Introduction: Our research group has directed its attention to the identification of structurally new vascular disrupting agents (VDAs) which are water soluble or may be converted into water soluble derivatives, possess vascular disrupting activity, and show antitumor activity at non- toxic doses. We prepared 1,5- and 1,2-diaryl-1H-imidazoles of general formula 1 and 2, respectively, which can be considered as cis-locked analogues of combretastatin A-4 (CA-4), a natural tubulin-binding VDA. We became interested in the imidazole core since its basic nitrogen atom may lead to compounds which can easily be formulated as water-soluble salts. Moreover, since the 3,4,5-trimethoxyphenyl substituted A ring of the CA-4 seems to be essential for the activity of this natural product, we maintained this moiety in compounds 1 and 2 and evaluated the effect due to the replacement of the B-ring of CA-4 with a variety of aryl substituents. Material and Methods: Imidazoles 1 and 2 were prepared using the innovative synthetic protocols we recently developed. The vascular disrupting activity of some selected compounds was evaluated in vitro on HUVEC, and in vivo on experimental tumors.
Bellina, Fabio; Cauteruccio, S; Borsotti, P; Taraboletti, G; Monti, S; Giavazzi, R; Rossi, R.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/107735
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