Concise syntheses of 7-anilino-indoline-N-benzenesulfonamides as antimitotic and vascular disrupting agents

Samir Mehndiratta, Yi-Fang Chiang, Mei-Jung Lai, Hsueh Yun Lee, Mei Chuan Chen, Ching-Chuan Kuo, Chi-Yen Chang, Jang-Yang Chang, Jing Ping Liou

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Described herein is the development of a novel series of 7-anilino-indoline-N-benzenesulfonamides, derived from ABT751 (1), as potent anticancer agents. Amongst the synthesized series, compounds 6, 12, 13, and 14 have shown comparable to better anticancer activity on comparing with compound 1. 7-(4-Cyanophenylamino)-1-(4-methoxybenzenesulfonyl)indoline (13) was found to be the most potent one with up to 6 fold better activity against KB, HT29, and MKN45 cancer cell lines with IC50 values of 49.7, 149, and 92 nM, respectively. Compound 13 was also found inhibiting multidrug resistant cancer cell lines, blocking cell cycle at G2/M phase, and inhibiting tubulin polymerization. Capillary disruption assay results revealed that compound 13 was able to disrupt formed capillaries in a concentration-dependent manner without affecting cell viability.

Original languageEnglish
Pages (from-to)4917-4923
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume22
Issue number17
DOIs
Publication statusPublished - Sep 1 2014

Fingerprint

Antimitotic Agents
Blood Vessels
Cells
Cell Line
G2 Phase
Tubulin
Polymerization
Cell Division
Antineoplastic Agents
Inhibitory Concentration 50
Neoplasms
Cell Survival
Cell Cycle
Assays
indoline
benzenesulfonamide
7-(4-cyanophenylamino)-1-(4-methoxybenzenesulfonyl)indoline
ABT751

Keywords

  • ABT751
  • Antimitotic
  • CA-4
  • Vascular-disrupting agents

ASJC Scopus subject areas

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

Cite this

Concise syntheses of 7-anilino-indoline-N-benzenesulfonamides as antimitotic and vascular disrupting agents. / Mehndiratta, Samir; Chiang, Yi-Fang; Lai, Mei-Jung; Lee, Hsueh Yun; Chen, Mei Chuan; Kuo, Ching-Chuan; Chang, Chi-Yen; Chang, Jang-Yang; Liou, Jing Ping.

In: Bioorganic and Medicinal Chemistry, Vol. 22, No. 17, 01.09.2014, p. 4917-4923.

Research output: Contribution to journalArticle

Mehndiratta, Samir ; Chiang, Yi-Fang ; Lai, Mei-Jung ; Lee, Hsueh Yun ; Chen, Mei Chuan ; Kuo, Ching-Chuan ; Chang, Chi-Yen ; Chang, Jang-Yang ; Liou, Jing Ping. / Concise syntheses of 7-anilino-indoline-N-benzenesulfonamides as antimitotic and vascular disrupting agents. In: Bioorganic and Medicinal Chemistry. 2014 ; Vol. 22, No. 17. pp. 4917-4923.
@article{469484d7f8b34ba9a3a60c97f645421e,
title = "Concise syntheses of 7-anilino-indoline-N-benzenesulfonamides as antimitotic and vascular disrupting agents",
abstract = "Described herein is the development of a novel series of 7-anilino-indoline-N-benzenesulfonamides, derived from ABT751 (1), as potent anticancer agents. Amongst the synthesized series, compounds 6, 12, 13, and 14 have shown comparable to better anticancer activity on comparing with compound 1. 7-(4-Cyanophenylamino)-1-(4-methoxybenzenesulfonyl)indoline (13) was found to be the most potent one with up to 6 fold better activity against KB, HT29, and MKN45 cancer cell lines with IC50 values of 49.7, 149, and 92 nM, respectively. Compound 13 was also found inhibiting multidrug resistant cancer cell lines, blocking cell cycle at G2/M phase, and inhibiting tubulin polymerization. Capillary disruption assay results revealed that compound 13 was able to disrupt formed capillaries in a concentration-dependent manner without affecting cell viability.",
keywords = "ABT751, Antimitotic, CA-4, Vascular-disrupting agents",
author = "Samir Mehndiratta and Yi-Fang Chiang and Mei-Jung Lai and Lee, {Hsueh Yun} and Chen, {Mei Chuan} and Ching-Chuan Kuo and Chi-Yen Chang and Jang-Yang Chang and Liou, {Jing Ping}",
year = "2014",
month = "9",
day = "1",
doi = "10.1016/j.bmc.2014.06.042",
language = "English",
volume = "22",
pages = "4917--4923",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "17",

}

TY - JOUR

T1 - Concise syntheses of 7-anilino-indoline-N-benzenesulfonamides as antimitotic and vascular disrupting agents

AU - Mehndiratta, Samir

AU - Chiang, Yi-Fang

AU - Lai, Mei-Jung

AU - Lee, Hsueh Yun

AU - Chen, Mei Chuan

AU - Kuo, Ching-Chuan

AU - Chang, Chi-Yen

AU - Chang, Jang-Yang

AU - Liou, Jing Ping

PY - 2014/9/1

Y1 - 2014/9/1

N2 - Described herein is the development of a novel series of 7-anilino-indoline-N-benzenesulfonamides, derived from ABT751 (1), as potent anticancer agents. Amongst the synthesized series, compounds 6, 12, 13, and 14 have shown comparable to better anticancer activity on comparing with compound 1. 7-(4-Cyanophenylamino)-1-(4-methoxybenzenesulfonyl)indoline (13) was found to be the most potent one with up to 6 fold better activity against KB, HT29, and MKN45 cancer cell lines with IC50 values of 49.7, 149, and 92 nM, respectively. Compound 13 was also found inhibiting multidrug resistant cancer cell lines, blocking cell cycle at G2/M phase, and inhibiting tubulin polymerization. Capillary disruption assay results revealed that compound 13 was able to disrupt formed capillaries in a concentration-dependent manner without affecting cell viability.

AB - Described herein is the development of a novel series of 7-anilino-indoline-N-benzenesulfonamides, derived from ABT751 (1), as potent anticancer agents. Amongst the synthesized series, compounds 6, 12, 13, and 14 have shown comparable to better anticancer activity on comparing with compound 1. 7-(4-Cyanophenylamino)-1-(4-methoxybenzenesulfonyl)indoline (13) was found to be the most potent one with up to 6 fold better activity against KB, HT29, and MKN45 cancer cell lines with IC50 values of 49.7, 149, and 92 nM, respectively. Compound 13 was also found inhibiting multidrug resistant cancer cell lines, blocking cell cycle at G2/M phase, and inhibiting tubulin polymerization. Capillary disruption assay results revealed that compound 13 was able to disrupt formed capillaries in a concentration-dependent manner without affecting cell viability.

KW - ABT751

KW - Antimitotic

KW - CA-4

KW - Vascular-disrupting agents

UR - http://www.scopus.com/inward/record.url?scp=84906935715&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906935715&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2014.06.042

DO - 10.1016/j.bmc.2014.06.042

M3 - Article

C2 - 25059503

AN - SCOPUS:84906935715

VL - 22

SP - 4917

EP - 4923

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 17

ER -