Concise syntheses of 7-anilino-indoline-N-benzenesulfonamides as antimitotic and vascular disrupting agents |
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| Institution: | 1. School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan;2. National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan;3. School of Pharmacy, National Defense Medical Center, 161 Minchuan East Road, Section 6, Taipei 114, Taiwan;4. Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan;5. Mackay Memorial Hospital, Taipei 10449, Taiwan;6. Ph.D Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan;1. Department of Chemistry, Bar Ilan University, Ramat Gan, Israel;2. Institute of Drug Research, The Hebrew University of Jerusalem, Ein Kerem, Jerusalem 91120, Israel;1. School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan;2. The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan;3. Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan;4. Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan;1. Organic Chemistry Laboratory, University Bayreuth, 95440 Bayreuth, Germany;2. Department of Molecular Structural Biology, Georg-August-University Göttingen, 37077 Göttingen, Germany;3. Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, 06120 Halle-Saale, Germany |
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| 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. |
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| Keywords: | ABT751 Vascular-disrupting agents Antimitotic CA-4 |
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