THE EFFECT OF CYCLIC HYDROXAMIC ACIDS ON ACTIVITY OF CА<sup>2</sup>+-ATPASE OF SARCOPLASMIC RETICULUM AND CYCLIC GUANOSINE MONOPHOSPHODIESTERASE

Abstract

Objective. The aim of the study was to research effect of new cyclic hydroxamic acids (CHA) I-VI on activity of Ca 2 +-ATPase of sarcoplasmic reticulum and cyclic guanosine monophosphodiesterase. Materials and methods. Activity of Ca 2 +-ATPase of sarcoplasmic reticulum and cyclic guanosine monophosphodiesterase has been evaluated. Results. It has been shown that at studied concentration (0.1 mM; 0.01 and 1 mM), CHA I-VI separate hydrolytic and transporting functions of Ca 2 +-ATPase of sarcoplasmic reticulum. Therefore, the antimetastatic effect of these compounds is assumed. Thus, at concentration of 0.1 mM, CHA inhibit active transport of calcium through the sarcoplasmic reticulum membrane by 40 ± 4 % (CHA-I), 50 ± 5% (CHA-II), 53 ± 5% (CHA-III), 70 ± 8% (CHA-V) and 75 ± 8% (CHA-VI) and inhibit hydrolysis of ATP by 20 ± 2%, 0 %, 0 %, 45 ± 5 % and 47 ± 3 % respectively. CHA-III, CHA-V and CHA-VI inhibit active transport of Са 2 + by 46 ± 5 %, 47 ± 5 % and 60 ± 6 %, and not inhibit or inhibit by 23 ± 2 % and 27 ± 3 % respectively, hydrolysis of ATP at concentration of 0.01 mM. CHA-V inhibits reversibly and non-competitively the hydrolytic function of Ca 2 +-ATPase of sarcoplasmic reticulum with K = 4 x 10 -5 M. All studied CHA inhibit activity of cyclic guanosine monophosphodiesterase at concentration of 0.1 mM, by less than 20 %. Conclusion. The data obtained predicts the antimetastatic activity of compounds CHA-II, CHA-III, CHA-V, CHA-VI. We recommend to study of CHA-II, CHA-III, CHA-V, CHA-VI on animal models as promising antimetastatic drugs.