Abstract
The effect of cyclic hydroxamic acids (CHAs) derived from glycine and D,L-alanine on the enzymatic activity of Ca 2+ ,Mg 2+ -ATPase of sarcoplasmic reticulum (SR Ca 2+ ,Mg 2+ -ATPase) and phosphodiesterase of cyclic guanosine monophosphate (cGMP PDE) has been investigated. CHAs I (C 5 H 10 N 2 O 2 ), II (C 6 H 1 2N 2 O 2 ), III (C 8 H 15 N 3 O 2 ), IV (C 9 H 17 N 3 O 2 ), V (C 11 H 21 N 3 O 2 ), and VI (C 12 H 23 N 3 O 2 ) are modulators of the SR Ca 2+ ,Mg 2+ -ATPase enzyme activity. Compounds I – VI separate the hydrolytic and transport functions of Ca 2+ ,Mg 2+ -ATPase to various degrees, thus violating the ratio of extra- and intracellular Ca 2+ ions that affects the adhesion of metastatic cells to a capillary endothelial tissue. Compounds IV and VI show maximum values of the index of metastases inhibition (IMI, %) for melanoma B-16 (amounting to 33 and 81%, respectively), which correlates with decreasing coefficient of transmembrane transfer of Ca 2+ ions to SR vesicles (equal to 0.95 for IV and 0.5 for VI) as compared to the [Ca 2+ ]/[ATP] ratio of 1.4 in the control. At the same time, CHAs I – VI do not affect the cGMP PDE function. The obtained experimental data allow potential antimetastatic drugs in the CHA family to be predicted.
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