Synthesis and biological evaluation of 2-indolinone derivatives as potential antitumor agents

Hongbin Zou; Liang Zhang; Jingfeng Ouyang; Marc A. Giulianotti; Yongping Yu

doi:10.1016/j.ejmech.2011.10.009

Synthesis and biological evaluation of 2-indolinone derivatives as potential antitumor agents

Hongbin Zou
, Liang Zhang
, Jingfeng Ouyang
, Marc A. Giulianotti
, Yongping Yu

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

Three series of 3-substituted-indolin-2-ones and azaindolin-2-ones have been synthesized and showed potential antiproliferative activity to cancer cell lines. The inhibition activities on VEGF-induced VEGFR phosphorylation were observed for selected 2-indolinones. Among the compounds synthesized, 5-fluoroindolin-2-one derivative 23 with a pyridone unit showed the most significant enzymatic and cellular activities. Flow cytometric analysis indicates that 23 plays a role in suppressing HCT-116 cell proliferation via G1 phase arrest and apoptosis in a dose dependent manner. The binding mode of compound 23 complexed with VEGFR-2 was predicted using FlexX algorithm. Described here are the chemistry and biological testing for these series which will guide the design and optimization of novel 2-indolione antitumor agents.

Original language	English (US)
Pages (from-to)	5970-5977
Number of pages	8
Journal	European Journal of Medicinal Chemistry
Volume	46
Issue number	12
DOIs	https://doi.org/10.1016/j.ejmech.2011.10.009
State	Published - Dec 2011
Externally published	Yes

Bibliographical note

Funding Information:
We thank the National Natural Sciences Foundation of China (No. 81072516, 20802066 ) and National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program” of China (No. 2009ZX09501-010 ) for the financial support.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

2-Indolinones
Antitumor agent
Apoptosis
VEGFR-2

Publisher link

10.1016/j.ejmech.2011.10.009

Find It

Find It at U of M Libraries

Cite this

@article{4241671e0b80422780abb9878612f414,

title = "Synthesis and biological evaluation of 2-indolinone derivatives as potential antitumor agents",

abstract = "Three series of 3-substituted-indolin-2-ones and azaindolin-2-ones have been synthesized and showed potential antiproliferative activity to cancer cell lines. The inhibition activities on VEGF-induced VEGFR phosphorylation were observed for selected 2-indolinones. Among the compounds synthesized, 5-fluoroindolin-2-one derivative 23 with a pyridone unit showed the most significant enzymatic and cellular activities. Flow cytometric analysis indicates that 23 plays a role in suppressing HCT-116 cell proliferation via G1 phase arrest and apoptosis in a dose dependent manner. The binding mode of compound 23 complexed with VEGFR-2 was predicted using FlexX algorithm. Described here are the chemistry and biological testing for these series which will guide the design and optimization of novel 2-indolione antitumor agents.",

keywords = "2-Indolinones, Antitumor agent, Apoptosis, VEGFR-2",

author = "Hongbin Zou and Liang Zhang and Jingfeng Ouyang and Giulianotti, \{Marc A.\} and Yongping Yu",

note = "Funding Information: We thank the National Natural Sciences Foundation of China (No. 81072516, 20802066 ) and National Science \& Technology Major Project {\textquotedblleft}Key New Drug Creation and Manufacturing Program{\textquotedblright} of China (No. 2009ZX09501-010 ) for the financial support. ",

year = "2011",

month = dec,

doi = "10.1016/j.ejmech.2011.10.009",

language = "English (US)",

volume = "46",

pages = "5970--5977",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

number = "12",

}

TY - JOUR

T1 - Synthesis and biological evaluation of 2-indolinone derivatives as potential antitumor agents

AU - Zou, Hongbin

AU - Zhang, Liang

AU - Ouyang, Jingfeng

AU - Giulianotti, Marc A.

AU - Yu, Yongping

N1 - Funding Information: We thank the National Natural Sciences Foundation of China (No. 81072516, 20802066 ) and National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program” of China (No. 2009ZX09501-010 ) for the financial support.

PY - 2011/12

Y1 - 2011/12

N2 - Three series of 3-substituted-indolin-2-ones and azaindolin-2-ones have been synthesized and showed potential antiproliferative activity to cancer cell lines. The inhibition activities on VEGF-induced VEGFR phosphorylation were observed for selected 2-indolinones. Among the compounds synthesized, 5-fluoroindolin-2-one derivative 23 with a pyridone unit showed the most significant enzymatic and cellular activities. Flow cytometric analysis indicates that 23 plays a role in suppressing HCT-116 cell proliferation via G1 phase arrest and apoptosis in a dose dependent manner. The binding mode of compound 23 complexed with VEGFR-2 was predicted using FlexX algorithm. Described here are the chemistry and biological testing for these series which will guide the design and optimization of novel 2-indolione antitumor agents.

AB - Three series of 3-substituted-indolin-2-ones and azaindolin-2-ones have been synthesized and showed potential antiproliferative activity to cancer cell lines. The inhibition activities on VEGF-induced VEGFR phosphorylation were observed for selected 2-indolinones. Among the compounds synthesized, 5-fluoroindolin-2-one derivative 23 with a pyridone unit showed the most significant enzymatic and cellular activities. Flow cytometric analysis indicates that 23 plays a role in suppressing HCT-116 cell proliferation via G1 phase arrest and apoptosis in a dose dependent manner. The binding mode of compound 23 complexed with VEGFR-2 was predicted using FlexX algorithm. Described here are the chemistry and biological testing for these series which will guide the design and optimization of novel 2-indolione antitumor agents.

KW - 2-Indolinones

KW - Antitumor agent

KW - Apoptosis

KW - VEGFR-2

UR - https://www.scopus.com/pages/publications/80955137715

UR - https://www.scopus.com/pages/publications/80955137715#tab=citedBy

U2 - 10.1016/j.ejmech.2011.10.009

DO - 10.1016/j.ejmech.2011.10.009

M3 - Article

C2 - 22019188

AN - SCOPUS:80955137715

SN - 0223-5234

VL - 46

SP - 5970

EP - 5977

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

IS - 12

ER -

Synthesis and biological evaluation of 2-indolinone derivatives as potential antitumor agents

Abstract

Bibliographical note

UN SDGs

Keywords

Publisher link

Find It

Other files and links

Fingerprint

Cite this