Synthesis and biological effects of new hybrid compounds composed of benzylguanidines and the alkylating group of busulfan on neuroblastoma cells |
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| Institution: | 1. Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstraße 21, D-79104 Freiburg, Germany;2. Children’s University Hospital, Hoppe-Seyler-Str.1, D-72076 Tübingen, Germany;1. Department of Chemistry, University of New Orleans, New Orleans, LA 70148, USA;2. Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA;3. Department of Pharmaceutical Sciences, University of California-Irvine, Irvine, CA 92697, USA;1. School of Chemistry, UNSW Australia, Sydney, NSW 2052, Australia;2. School of Chemistry, The University of Sydney, NSW 2006, Australia;3. Eskitis Institute for Drug Discovery, Griffith University, Nathan, QLD 4111, Australia;1. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People’s Republic of China;2. School of Chemical Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei, Nanjing 210094, People’s Republic of China;1. Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States;2. Neuroscience Discovery Biology, Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States |
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| Abstract: | 131Iodine-labelled (meta-iodobenzyl)guanidine (131I]-mIBG) and busulfan butane-1,4-diylbis(methanesulfonate)] are well-established pharmaceuticals in neuroblastoma therapy. We report the design, synthesis, and testing of hybrid molecules—mBBG and pBBG—which combine key structural features of (meta-iodobenzyl)guanidine and busulfan: they contain a benzylguanidine moiety for accumulating in neuroblastoma cells via the noradrenaline transporter and, in the meta- or para-position, respectively, one of the two identical alkylating motives of busulfan for killing cells. Uptake and toxicity of hybrids mBBG and pBBG in human neuroblastoma cells compared favorably to their ancestors 131I]-mIBG and busulfan. |
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| Keywords: | Neuroblastoma Alkylating agent Busulfan |
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