Novel microtubule-interacting phenoxy pyridine and phenyl sulfanyl pyridine analogues for cancer therapy

Ravi Anchoori, Madeleine Susanne Quirine Kortenhorst, Manuel Hidalgo, Taradas Sarkar, Gurulingappa Hallur, Ruoli Bai, Paul J. Van Diest, Ernest Hamel, Saeed R. Khan

Research output: Contribution to journalArticle

Abstract

Current microtubule inhibitory agents used in the clinic to treat cancer have severe side effects, and development of resistance is frequent. We have evaluated the antitumor effect of a novel 30-compound library of phenoxy pyridine and phenyl sulfanyl pyridine derivatives. MTT assays revealed that, of all 30 compounds tested, compounds 2 and 3 showed the largest decrease in proliferation (low μM range) against Panc1 and HS766T human pancreatic cancer cells. Flow cytometry experiments with MCF7 breast cancer cells showed a G2/M arrest comparable to that of colcemid. Immunofluorescence staining demonstrated complete disappearance of intracellular microtubules. Tubulin assembly assays, however, showed a dose-dependent decrease in tubulin assembly with compound 3 that seemed limited to about 50% of the control reaction. With compound 2 treatment, there was only a delay in the onset of assembly, with no effect on the extent of the reaction. Taken together, our results show that these novel microtubule inhibitors have promising anticancer activity and can be potentially used to overcome paclitaxel resistance in the clinical setting.

Original languageEnglish (US)
Pages (from-to)5953-5957
Number of pages5
JournalJournal of Medicinal Chemistry
Volume51
Issue number19
DOIs
StatePublished - Oct 9 2008

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Microtubules
Tubulin
Demecolcine
Neoplasms
Paclitaxel
Pancreatic Neoplasms
Libraries
Fluorescent Antibody Technique
Flow Cytometry
Therapeutics
Staining and Labeling
Breast Neoplasms
pyridine
compound 30

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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Novel microtubule-interacting phenoxy pyridine and phenyl sulfanyl pyridine analogues for cancer therapy. / Anchoori, Ravi; Kortenhorst, Madeleine Susanne Quirine; Hidalgo, Manuel; Sarkar, Taradas; Hallur, Gurulingappa; Bai, Ruoli; Van Diest, Paul J.; Hamel, Ernest; Khan, Saeed R.

In: Journal of Medicinal Chemistry, Vol. 51, No. 19, 09.10.2008, p. 5953-5957.

Research output: Contribution to journalArticle

Anchoori, R, Kortenhorst, MSQ, Hidalgo, M, Sarkar, T, Hallur, G, Bai, R, Van Diest, PJ, Hamel, E & Khan, SR 2008, 'Novel microtubule-interacting phenoxy pyridine and phenyl sulfanyl pyridine analogues for cancer therapy', Journal of Medicinal Chemistry, vol. 51, no. 19, pp. 5953-5957. https://doi.org/10.1021/jm800203e
Anchoori, Ravi ; Kortenhorst, Madeleine Susanne Quirine ; Hidalgo, Manuel ; Sarkar, Taradas ; Hallur, Gurulingappa ; Bai, Ruoli ; Van Diest, Paul J. ; Hamel, Ernest ; Khan, Saeed R. / Novel microtubule-interacting phenoxy pyridine and phenyl sulfanyl pyridine analogues for cancer therapy. In: Journal of Medicinal Chemistry. 2008 ; Vol. 51, No. 19. pp. 5953-5957.
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AU - Hallur, Gurulingappa

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AU - Van Diest, Paul J.

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