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Cyclic hydroxamic acids derived from α-amino acids 1. Regioselective synthesis, structure, NO-donor and antimetastatic activities of spirobicyclic hydroxamic acids derived from glycine and DL-alanine

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Abstract

The reactions of glycine hydroxamic and DL-alanine hydroxamic acids with triacetonamine are chemoselective and afford 1-hydroxy-7,7,9,9-tetramethyl-1,4,8-triazaspiro[4.5]decan-2-one (3) and (±)-1-hydroxy-3,7,7,9,9-pentamethyl-1,4,8-triazaspiro[4.5]decan-2-one (4), respectively. The X-ray diffraction study showed that compound 3 crystallizes as a solvate with MeCN (1: 1). As shown by ESR measurements, spiro hydroxamic acids 3 and 4 are NO donors in in vitro biological systems. The NO-donor activity of compounds 3 and 4 was found to be substantially higher in the presence of DMSO. Homologue 4 is a stronger NO donor than 3. Compound 4 also exhibits high antimetastatic activity (81%) on the B16-melanoma model.

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Authors and Affiliations

  1. Institute of Problems of Chemical Physics, Russian Academy of Sciences, 1 prosp. Akad. Semenova, 142432, Chernogolovka, Moscow Region, Russian Federation

    I. V. Vystorop, N. P. Konovalova, V. N. Varfolomeev, B. S. Fedorov, T. E. Sashenkova & E. N. Berseneva

  2. A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 ul. Vavilova, 119991, Moscow, Russian Federation

    Yu. V. Nelyubina & K. A. Lyssenko

  3. N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 4 ul. Kosygina, 119991, Moscow, Russian Federation

    R. G. Kostyanovsky

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  1. I. V. Vystorop
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  2. N. P. Konovalova
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  3. Yu. V. Nelyubina
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  4. V. N. Varfolomeev
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  5. B. S. Fedorov
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  6. T. E. Sashenkova
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  7. E. N. Berseneva
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  8. K. A. Lyssenko
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  9. R. G. Kostyanovsky
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Correspondence to I. V. Vystorop.

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Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 127–134, January, 2010.

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Vystorop, I.V., Konovalova, N.P., Nelyubina, Y.V. et al. Cyclic hydroxamic acids derived from α-amino acids 1. Regioselective synthesis, structure, NO-donor and antimetastatic activities of spirobicyclic hydroxamic acids derived from glycine and DL-alanine. Russ Chem Bull 59, 127–135 (2010). https://doi.org/10.1007/s11172-010-0055-x

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