2. Academic Validation
  3. Concise syntheses of 7-anilino-indoline-N-benzenesulfonamides as antimitotic and vascular disrupting agents

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

  • Bioorg Med Chem. 2014 Sep 1;22(17):4917-23. doi: 10.1016/j.bmc.2014.06.042.
Samir Mehndiratta 1,  Yi-Fang Chiang 2,  Mei-Jung Lai 1,  Hsueh-Yun Lee 1,  Mei-Chuan Chen 3,  Ching-Chuan Kuo 4,  Chi-Yen Chang 4,  Jang-Yang Chang 5,  Jing-Ping Liou 6
Affiliations

Affiliations

  • 1 School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan.
  • 2 School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan; Mackay Memorial Hospital, Taipei 10449, Taiwan.
  • 3 Ph.D Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan.
  • 4 National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan.
  • 5 National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan; Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: [email protected].
  • 6 School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan; School of Pharmacy, National Defense Medical Center, 161 Minchuan East Road, Section 6, Taipei 114, Taiwan. Electronic address: [email protected].
PMID: 25059503 DOI: 10.1016/j.bmc.2014.06.042
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 92nM, 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.

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