One-pot regioselective synthesis of tetrahydroindazolones and evaluation of their antiproliferative and Src kinase inhibitory activities

V. Kameshwara Rao, Bhupender S. Chhikara, Rakesh Tiwari, Amir Nasrolahi Shirazi, Keykavous Parang, Anil Kumar

Research output: Contribution to journalArticle

Abstract

A number of 2-substituted tetrahydroindazolones were synthesized by three-component condensation reaction of 1,3-diketones, substituted hydrazines, benzaldehydes, and Yb(OTf) 3 as a catalyst in [bmim][BF 4] ionic liquid using a simple, efficient, and economical one-pot method. The synthesized tetrahydroindazolones were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), human ovarian adenocarcinoma (SK-OV-3), and c-Src kinase activity. 3,4-Dichlorophenyl tetrahydroindazolone derivative (15) inhibited the cell proliferation of HT-29 and SK-OV-3 cells by 62% and 58%, respectively. 2,3-Diphenylsubstituted tetrahydroindazolone derivatives, 19, 25, and 33, inhibited the cell proliferation of HT-29 cells by 65-72% at a concentration of 50 μM. In general, the tetrahydroindazolones showed modest inhibition of c-Src kinase where 4-tertbutylphenyl- (32) and 3,4-dichlorophenyl- (13) derivatives showed the inhibition of c-Src kinase with IC 50 values of 35.1 and 50.7 μM, respectively.

Original languageEnglish (US)
Pages (from-to)410-414
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

Fingerprint

src-Family Kinases
Cell proliferation
Cell Proliferation
Derivatives
Benzaldehydes
Hydrazines
Ionic Liquids
HT29 Cells
Condensation reactions
Colon
Adenocarcinoma
Carcinoma
Catalysts
CSK tyrosine-protein kinase

Keywords

  • Antiproliferative
  • Cell proliferation
  • Inhibitor
  • Src kinase
  • Tetrahydroindazolones

ASJC Scopus subject areas

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

Cite this

One-pot regioselective synthesis of tetrahydroindazolones and evaluation of their antiproliferative and Src kinase inhibitory activities. / Rao, V. Kameshwara; Chhikara, Bhupender S.; Tiwari, Rakesh; Shirazi, Amir Nasrolahi; Parang, Keykavous; Kumar, Anil.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 22, No. 1, 01.01.2012, p. 410-414.

Research output: Contribution to journalArticle

Rao, V. Kameshwara ; Chhikara, Bhupender S. ; Tiwari, Rakesh ; Shirazi, Amir Nasrolahi ; Parang, Keykavous ; Kumar, Anil. / One-pot regioselective synthesis of tetrahydroindazolones and evaluation of their antiproliferative and Src kinase inhibitory activities. In: Bioorganic and Medicinal Chemistry Letters. 2012 ; Vol. 22, No. 1. pp. 410-414.
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