Design, synthesis, and antiproliferative and CDK2-cyclin a inhibitory activity of novel flavopiridol analogues

Yu Mi Ahn, Lakshminarayana Vogeti, Chun Jing Liu, Hari K R Santhapuram, Jonathan M. White, Veena Vasandani, Lester A. Mitscher, Gerald H. Lushington, Paul R. Hanson, Douglas R. Powell, Richard H. Himes, Katherine F. Roby, Qizhuang Ye, Gunda I. Georg

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The design and synthesis of a small library of 8-amidoflavone, 8-sulfonamidoflavone, 8-amido-7-hydroxyflavone, and heterocyclic analogues of flavopiridol is reported. The potential activity of these compounds as kinase inhibitors was evaluated by cytotoxicity studies in MCF-7 and ID-8 cancer cell lines and inhibition of CDK2-Cyclin A enzyme activity in vitro. The antiproliferative and CDK2-Cyclin A inhibitory activity of these analogues was significantly lower than the activity of flavopiridol. Molecular docking simulations were carried out and these studies suggested a different binding orientation inside the CDK2 binding pocket for these analogues compared to flavopiridol.

Original languageEnglish (US)
Pages (from-to)702-713
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume15
Issue number2
DOIs
StatePublished - Jan 15 2007
Externally publishedYes

Fingerprint

alvocidib
Cyclins
Cyclin A
Molecular Docking Simulation
Enzyme inhibition
Enzyme activity
Cytotoxicity
Libraries
Phosphotransferases
Cells
Cell Line
Enzymes
Neoplasms

Keywords

  • CDK2-Cyclin A
  • Cytotoxicity
  • Docking simulations
  • Flavopiridol analogues
  • Synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Ahn, Y. M., Vogeti, L., Liu, C. J., Santhapuram, H. K. R., White, J. M., Vasandani, V., ... Georg, G. I. (2007). Design, synthesis, and antiproliferative and CDK2-cyclin a inhibitory activity of novel flavopiridol analogues. Bioorganic and Medicinal Chemistry, 15(2), 702-713. https://doi.org/10.1016/j.bmc.2006.10.063

Design, synthesis, and antiproliferative and CDK2-cyclin a inhibitory activity of novel flavopiridol analogues. / Ahn, Yu Mi; Vogeti, Lakshminarayana; Liu, Chun Jing; Santhapuram, Hari K R; White, Jonathan M.; Vasandani, Veena; Mitscher, Lester A.; Lushington, Gerald H.; Hanson, Paul R.; Powell, Douglas R.; Himes, Richard H.; Roby, Katherine F.; Ye, Qizhuang; Georg, Gunda I.

In: Bioorganic and Medicinal Chemistry, Vol. 15, No. 2, 15.01.2007, p. 702-713.

Research output: Contribution to journalArticle

Ahn, YM, Vogeti, L, Liu, CJ, Santhapuram, HKR, White, JM, Vasandani, V, Mitscher, LA, Lushington, GH, Hanson, PR, Powell, DR, Himes, RH, Roby, KF, Ye, Q & Georg, GI 2007, 'Design, synthesis, and antiproliferative and CDK2-cyclin a inhibitory activity of novel flavopiridol analogues', Bioorganic and Medicinal Chemistry, vol. 15, no. 2, pp. 702-713. https://doi.org/10.1016/j.bmc.2006.10.063
Ahn, Yu Mi ; Vogeti, Lakshminarayana ; Liu, Chun Jing ; Santhapuram, Hari K R ; White, Jonathan M. ; Vasandani, Veena ; Mitscher, Lester A. ; Lushington, Gerald H. ; Hanson, Paul R. ; Powell, Douglas R. ; Himes, Richard H. ; Roby, Katherine F. ; Ye, Qizhuang ; Georg, Gunda I. / Design, synthesis, and antiproliferative and CDK2-cyclin a inhibitory activity of novel flavopiridol analogues. In: Bioorganic and Medicinal Chemistry. 2007 ; Vol. 15, No. 2. pp. 702-713.
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