Efficient synthesis and cell migration inhibitory effect of substituted benzamidothiazolylpyrazole-capped AWD*I-NH2 |
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| Affiliation: | 1. Department of Chemistry, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan, Hubei 430081, PR China;2. School of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, Hubei 430081, PR China;3. Department of Dermatology, Biochemistry and Molecular Medicine, University of California Davis, School of Medicine, Sacramento, CA, United States;1. Center for Intelligent Chemical Instrumentation, Department of Chemistry and Biochemistry, Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA;2. Department of Forensic Science, Jiangsu Police Institute, Nanjing, Jiang Su, 210031, China;3. Department of Chemistry and Biochemistry, Department of Biological Chemistry, David Geffen School of Medicine at UCLA, and UCLA/DOE Institute for Genomics and Proteomics, University of California-Los Angeles, Los Angeles, CA 90095, USA;1. School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, GPO Box U1987, Perth, Western Australia 6845, Australia;2. School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia;1. Laboratoire des Mécanismes Réactionnels, Département de Chimie, Ecole Polytechnique and CNRS, 91128 Palaiseau Cedex, France;2. Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense, Denmark;1. Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK;2. Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK;1. Department of Anatomy and Cell Biology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan;2. Clean Energy Research Center, University of Yamanashi, Kofu, Yamanashi 400-8510, Japan;3. Department of Surgery, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan;4. Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Kofu, Yamanashi 400-8510, Japan;5. Faculty of Science and Engineering, Waseda University, Shinjuku, Tokyo 169-0072, Japan;6. Institute of Statistical Mathematics, Research Organization for Information and Systems, Tachikawa, Tokyo 190-8562, Japan;1. Shaanxi Key Lab Basic & New Herbal Medicament Research Center, College of Pharmacy, Shaanxi University of Chinese Medicine, China;2. Shenzhen Neptunus Medical Science and Technology Research Institute, Shenzhen, China;3. State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Chemistry, Nankai University, Tianjin, China;4. Yantai Institute of Materia Medica, Yantai Key Laboratory of Nanomedicine &Advanced Preparations, Yantai, China |
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| Abstract: | Substituted (2-benzamidothiazol-5-yl)pyrazole-capped AWD*I-NH2 were synthesized and their antimigration activity was studied. The improved efficiency and scalability of the analog synthesis was achieved via a late-stage diversification of the benzoyl group and a convergent route in which the bisazole capping agents and off-resin peptide AWD*I-NH2 were prepared in parallel and coupled together in solution at the last step. Bioassay results indicate that all the peptidomimetics can significantly inhibit the migration of breast cancer cells MDA-MB-231 but possess no apparent cytotoxicity. In general, the antimigration potency of the peptidomimetics is correlated to the electron-withdrawing capacity of the substituents on the terminal phenyl ring. The inhibitory effect shows dose-dependent and holds also against lung and cervical cancer cells. The level of f-actin was reduced dramatically in cells treated with the inhibitor, suggesting that the migration inhibitory effect is related to the disruption of cell locomotive protrusions. |
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| Keywords: | Cell migration Inhibition Peptidomimetics Synthesis f-Actin |
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