Synthesis, Cytotoxicity, and Genotoxicity of 10-Aza-9-oxakalkitoxin, an N,N,O-Trisubstituted Hydroxylamine Analog, or Hydroxalog, of a Marine Natural Product
| Autor: | Christopher A. Rice, Scott D. Pegan, Joseph Media, Sandeep Dhanju, Kapil Upadhyaya, Frederick A. Valeriote, David Crich |
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| Rok vydání: | 2020 |
| Předmět: |
Kalkitoxin
Natural product Stereochemistry Chemistry General Chemistry 010402 general chemistry medicine.disease_cause 01 natural sciences Biochemistry Catalysis 0104 chemical sciences chemistry.chemical_compound Colloid and Surface Chemistry Hydroxylamine Cell culture medicine Moiety Cytotoxicity IC50 Genotoxicity |
| Zdroj: | Journal of the American Chemical Society. 142:9147-9151 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.0c03763 |
| Popis: | We describe the synthesis of 10-aza-9-oxakalkitoxin, an N,N,O-trisubstituted hydroxylamine-based analog, or hydroxalog, of the cytotoxic marine natural product kalkitoxin in which the -NMe-O- moiety replaces a -CHMe-CH2- unit in the backbone of the natural product. 10-Aza-9-oxakalkitoxin displays potent and selective cytotoxicity (IC50 2.4 ng mL-1) comparable to that of kalkitoxin itself (IC50 3.2 ng mL-1) against the human hepato-carcinoma cell line HepG2 over both the human leukemia cell line CEM and the normal hematopoietic CFU-GM. Like kalkitoxin, and contrary to the common expectation for hydroxylamines, 10-aza-9-oxakalkitoxin is not mutagenic. |
| Databáze: | OpenAIRE |
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