New Spirocyclic Hydroxamic Acids as Effective Antiproliferative Agents.

AIMS The main goal of this work where is to synthesize new original spirocyclic hydroxamic acids, investigate their cytotoxicity against to the panel of tumor cell lines and possible mechanism of action of these active compounds. BACKGROUND Hydroxamic acids are one of the promising classes of chemical compounds with proven has anticancer potential properties. This is manifested in the presence of metal chelating and antioxidant activities, the ability to inhibit histone deacetylase enzymes and a chemosensitizing effect against well known cytostatics. OBJECTIVE Original spirocyclic hydroxamic acids were synthesized and spectrums of their antiproliferative activities were investigated. METHODS The cytotoxic activities on different tumor lines (SH-SY5Y, HeLa and healthy cells HEK-293) were investigated and determined possible underlying mechanisms of their activity. RESULT New original spirocyclic hydroxamic acids were synthesized. These compounds exhibit antiproliferative properties against of the various tumor cultures cells and also exhibits antioxidant activity, a depolarizing effect on the mitochondrial membrane, inhibit the activity of the histone deacetylase enzyme, and also decrease of basal glycolysis and glycolytic capacity reserve of HeLa and SH-SY5Y tumor cell lines. CONCLUSION The most promising are compounds 5j-l containing two chlorine atoms as substituents in the quinazoline part of the molecule and hydroxamate function. Therefore, these compounds can be considered as hit compounds for the development on their basis multi-target anticancer agents.