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 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.
authors: School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan.
authors: Samir
authors: S
authors: Mehndiratta
authors: School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan; Mackay Memorial Hospital, Taipei 10449, Taiwan.
authors: Yi-Fang
authors: YF
authors: Chiang
authors: School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan.
authors: Mei-Jung
authors: MJ
authors: Lai
authors: School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan.
authors: Hsueh-Yun
authors: HY
authors: Lee
authors: Ph.D Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan.
authors: Mei-Chuan
authors: MC
authors: Chen
authors: National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan.
authors: Ching-Chuan
authors: CC
authors: Kuo
authors: National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan.
authors: Chi-Yen
authors: CY
authors: Chang
authors: 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: jychang@nhri.org.tw.
authors: Jang-Yang
authors: JY
authors: Chang
authors: 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: jpl@tmu.edu.tw.
authors: Jing-Ping
authors: JP
authors: Liou
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002196:Capillaries / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007624:KB Cells; D008938:Mitosis / Q000187:drug effects*; D015394:Molecular Structure; D058105:Polymerization / Q000187:drug effects; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000596489:7-(4-cyanophenylamino)-1-(4-methoxybenzenesulfonyl)indoline; D000970:Antineoplastic Agents; D007211:Indoles; D013449:Sulfonamides; D014404:Tubulin; D050257:Tubulin Modulators
keywords: ABT751; Antimitotic; CA-4; Vascular-disrupting agents