Organometallic Nucleosides: Synthesis and Biological Evaluation of Substituted Dicobalt Hexacarbonyl 2′‐Deoxy‐5‐oxopropynyluridines
نویسندگان
چکیده
Reactions of dicobalt octacarbonyl [Co2(CO)8] with 2'-deoxy-5-oxopropynyluridines and related compounds gave dicobalt hexacarbonyl nucleoside complexes (83-31 %). The synthetic outcomes were confirmed by X-ray structure determination of dicobalt hexacarbonyl 2'-deoxy-5-(4-hydroxybut-1-yn-1-yl)uridine, which exhibits intermolecular hydrogen bonding between a modified base and ribose. The electronic structure of this compound was characterized by the DFT calculations. The growth inhibition of HeLa and K562 cancer cell lines by organometallic nucleosides was examined and compared to that by alkynyl nucleoside precursors. Coordination of the dicobalt carbonyl moiety to the 2'-deoxy-5-alkynyluridines led to a significant increase in the cytotoxic potency. The cobalt compounds displayed antiproliferative activities with median inhibitory values (IC50) in the range of 20 to 80 μm for the HeLa cell line and 18 to 30 μm for the K562 cell line. Coordination of an acetyl-substituted cobalt nucleoside was expanded by using the 1,1-bis(diphenylphosphino)methane (dppm) ligand, which exhibited cytotoxicity at comparable levels. The formation of reactive oxygen species in the presence of cobalt compounds was determined in K562 cells. The results indicate that the mechanism of action for most antiproliferative cobalt compounds may be related to the induction of oxidative stress.
منابع مشابه
Cover Feature: Organometallic Nucleosides: Synthesis and Biological Evaluation of Substituted Dicobalt Hexacarbonyl 2′‐Deoxy‐5‐oxopropynyluridines (ChemistryOpen 3/2018)
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ATTEMPTED SYNTHESIS OF 5' - DEOXY - 5' - PHOSPHONO - ISOCYTIDINE SYNTHESIS OF PHOSPHONIC ACID DERIVATIVES OF ACYCLO - NUCLEOSIDES. PREPARATION OF 1- ?- D- ARABINOFURANOSYL PYRIMIDINES
The synthesis of 5' - deoxynucleoside 5' - phosphonates which contains a 5' - CP bond in place of the 5' -COP bond of the naturally occuring nucleotides is described. The preparation of phosphonate derivatives of acyclo - nucleosides and a simple method for the conversion of 1-? -D-ribofuranosyl pyrimidines to the corresponding 1-? -D-arabinofuranosyl pyrimidines are also explained
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