Vascular disrupting activity of tubulin-binding 1,5-diaryl-1H-imidazoles

Katiuscia Bonezzi, Giulia Taraboletti, Patrizia Borsotti, Fabio Bellina, Renzo Rossi, Raffaella Giavazzi

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Highly cytotoxic 1,5-diaryl-1H-imidazoles were studied to clarify the relationship between cytotoxicity and activity as vascular disrupting agents (VDA). All the compounds disorganized the tubulin cytoskeleton, affected endothelial cell morphology and capillary formation in vitro, and caused vessel shutdown and tumor necrosis in vivo, thus confirming their vascular disrupting properties. Nonetheless, the substitution patterns on the imidazole ring, responsible for greater interaction energy with tubulin and higher cytotoxicity, were not associated to greater vascular disrupting activity.

Original languageEnglish
Pages (from-to)7906-7910
Number of pages5
JournalJournal of Medicinal Chemistry
Volume52
Issue number23
DOIs
Publication statusPublished - Dec 10 2009

Fingerprint

Imidazoles
Tubulin
Blood Vessels
Cytoskeleton
Necrosis
Endothelial Cells
Neoplasms

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Vascular disrupting activity of tubulin-binding 1,5-diaryl-1H-imidazoles. / Bonezzi, Katiuscia; Taraboletti, Giulia; Borsotti, Patrizia; Bellina, Fabio; Rossi, Renzo; Giavazzi, Raffaella.

In: Journal of Medicinal Chemistry, Vol. 52, No. 23, 10.12.2009, p. 7906-7910.

Research output: Contribution to journalArticle

Bonezzi, Katiuscia ; Taraboletti, Giulia ; Borsotti, Patrizia ; Bellina, Fabio ; Rossi, Renzo ; Giavazzi, Raffaella. / Vascular disrupting activity of tubulin-binding 1,5-diaryl-1H-imidazoles. In: Journal of Medicinal Chemistry. 2009 ; Vol. 52, No. 23. pp. 7906-7910.
@article{a164c12543de45d7beabecc3f63dbeda,
title = "Vascular disrupting activity of tubulin-binding 1,5-diaryl-1H-imidazoles",
abstract = "Highly cytotoxic 1,5-diaryl-1H-imidazoles were studied to clarify the relationship between cytotoxicity and activity as vascular disrupting agents (VDA). All the compounds disorganized the tubulin cytoskeleton, affected endothelial cell morphology and capillary formation in vitro, and caused vessel shutdown and tumor necrosis in vivo, thus confirming their vascular disrupting properties. Nonetheless, the substitution patterns on the imidazole ring, responsible for greater interaction energy with tubulin and higher cytotoxicity, were not associated to greater vascular disrupting activity.",
author = "Katiuscia Bonezzi and Giulia Taraboletti and Patrizia Borsotti and Fabio Bellina and Renzo Rossi and Raffaella Giavazzi",
year = "2009",
month = "12",
day = "10",
doi = "10.1021/jm900968s",
language = "English",
volume = "52",
pages = "7906--7910",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "23",

}

TY - JOUR

T1 - Vascular disrupting activity of tubulin-binding 1,5-diaryl-1H-imidazoles

AU - Bonezzi, Katiuscia

AU - Taraboletti, Giulia

AU - Borsotti, Patrizia

AU - Bellina, Fabio

AU - Rossi, Renzo

AU - Giavazzi, Raffaella

PY - 2009/12/10

Y1 - 2009/12/10

N2 - Highly cytotoxic 1,5-diaryl-1H-imidazoles were studied to clarify the relationship between cytotoxicity and activity as vascular disrupting agents (VDA). All the compounds disorganized the tubulin cytoskeleton, affected endothelial cell morphology and capillary formation in vitro, and caused vessel shutdown and tumor necrosis in vivo, thus confirming their vascular disrupting properties. Nonetheless, the substitution patterns on the imidazole ring, responsible for greater interaction energy with tubulin and higher cytotoxicity, were not associated to greater vascular disrupting activity.

AB - Highly cytotoxic 1,5-diaryl-1H-imidazoles were studied to clarify the relationship between cytotoxicity and activity as vascular disrupting agents (VDA). All the compounds disorganized the tubulin cytoskeleton, affected endothelial cell morphology and capillary formation in vitro, and caused vessel shutdown and tumor necrosis in vivo, thus confirming their vascular disrupting properties. Nonetheless, the substitution patterns on the imidazole ring, responsible for greater interaction energy with tubulin and higher cytotoxicity, were not associated to greater vascular disrupting activity.

UR - http://www.scopus.com/inward/record.url?scp=72249107517&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72249107517&partnerID=8YFLogxK

U2 - 10.1021/jm900968s

DO - 10.1021/jm900968s

M3 - Article

VL - 52

SP - 7906

EP - 7910

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 23

ER -