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

doi:10.1016/j.bmcl.2011.10.124

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 journal › Article › peer-review

17 Scopus citations

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 language	English (US)
Pages (from-to)	410-414
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	1
DOIs	https://doi.org/10.1016/j.bmcl.2011.10.124
State	Published - Jan 1 2012
Externally published	Yes

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

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title = "One-pot regioselective synthesis of tetrahydroindazolones and evaluation of their antiproliferative and Src kinase inhibitory activities",

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.",

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author = "Rao, {V. Kameshwara} and Chhikara, {Bhupender S.} and Rakesh Tiwari and Shirazi, {Amir Nasrolahi} and Keykavous Parang and Anil Kumar",

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AU - Rao, V. Kameshwara

AU - Chhikara, Bhupender S.

AU - Tiwari, Rakesh

AU - Shirazi, Amir Nasrolahi

AU - Parang, Keykavous

AU - Kumar, Anil

PY - 2012/1/1

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N2 - 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.

AB - 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.

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KW - Cell proliferation

KW - Inhibitor

KW - Src kinase

KW - Tetrahydroindazolones

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

Abstract

Keywords

ASJC Scopus subject areas

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