DL-valine cyclic hydroxamic acid: Synthesis and potential chemosensitizing antitumor action

The reaction of DL-valine hydroxamic acid with triacetonamine passes as N, N′-regioselective cyclocondensation to form (±) -1-hydroxy-3-isopropyl-7,7,9,9-tetramethyl-1,4,8-triazaspiro [4.5] decan-2-one. In vivo study of chemosensitizing antitumor activity of spirocyclic hydroxamic acid by the combination therapy with cytostatics of alkylating type cisplatin and cyclophosphamide in the model of leukemia P388 was investigated. It was shown the ability of this acid to increase the sensitivity of the tumor to the action of cisplatin and cyclophosphamide applied at doses below therapeutic. Chemosensitizing activity of spirocyclic hydroxamic acid has made it possible to achieve an appreciable level of survival of tumor-bearing animals (up to 37.5%).