Lipid peroxide (LPO) plays pivotal roles in the process and development of many diseases. In this work, we studied the inhibitory effect of probimane (Pro), a Chinese anticancer agent, on erythrocyte LPO and the inter...Lipid peroxide (LPO) plays pivotal roles in the process and development of many diseases. In this work, we studied the inhibitory effect of probimane (Pro), a Chinese anticancer agent, on erythrocyte LPO and the interaction of Pro with sialic acids (sia). Malondialdehyde (MDA) of erythrocytes activated by hydrogen peroxide was measured. Pro was found to inhibit the product of LPO induced by hydrogen peroxide in a non-enzyme system of both rabbit and human erythrocytes in the absence of doxorubicin. Sia were found to enhance LPO production and the activity of N-glycolylneuraminic acid (NeuGc) was about 5 times higher than that of N-acetylneuraminic acid (5AcNeu) at equivalent concentrations. Pro inhibited the increased LPO production induced by sia and the activity of Pro against LPO with 5AcNeu was almost twofold higher than that of Pro alone. It suggests that Pro be an inhibitor of LPO (free radicals) and as a functional modulator of sia in body.展开更多
To clarify the possible mechanisms of α anordin and probimane on calmodulin Ca^(++)-Mg^(++)-ATPase system, enzyme dynamic study was carried out by determining three dynamic parameters [the substrate concentration(AT...To clarify the possible mechanisms of α anordin and probimane on calmodulin Ca^(++)-Mg^(++)-ATPase system, enzyme dynamic study was carried out by determining three dynamic parameters [the substrate concentration(ATP) response curve, dose(inhibitors) response curve and time response curve]. Our data have shown that the inhibitory rates of α anordrin and probimane are unrelated to substrate(APT) concentrations, but related to calmodulin concentrations. The inhibition of α anordrin and probimane is very quick that is completed within 1 to 5 min and can maintain more than 1 hr in the same inhibitory rates. So it is possible that α anordrin and probimane are calmodulin competitors with calmodulin like binding whose actions can occur by affecting the reaction balance of substrate and product on target enzymes of calmodulin( Ca^(++)-Mg^(++)-ATPase).展开更多
To investigate the influence of probimane on the lipoperoxidation of human red cells in vitro. Malondialdehyde (MDA) of human red cells induced by hydrogen peroxide was assayed by means of colorimetry. It was show...To investigate the influence of probimane on the lipoperoxidation of human red cells in vitro. Malondialdehyde (MDA) of human red cells induced by hydrogen peroxide was assayed by means of colorimetry. It was shown that probimane ( > 2 μM ) could inhibit the lipoperoxidation without adriamycin. The inhibitory rates of probimane were 9.3 % ( 2 μM ) and 35.3 % ( 10 μM ) respectively ( P< 0.05). Probimane ( 2 μM ) inhibited lipoperoxidation in the presence of sialic acid ( 0.4 μM ) ( inhibitory rate 17.8 % ) was approximately two fold higher than those without sialic acid ( inhibitory rate 9.3 % ). So probimane may inhibit tumor growth through affecting lipoperoxidations and exhibit anticancer effects via sialic acids.展开更多
The ring-and side-chain-<sup>14</sup>C-labeled probimane, 1,2-bis （4-morpholinomethy1-3,5-dioxopiperazin-1-yl） propane were synthesized from acetic acid-1-<sup>14</sup>C in 4 steps and from &...The ring-and side-chain-<sup>14</sup>C-labeled probimane, 1,2-bis （4-morpholinomethy1-3,5-dioxopiperazin-1-yl） propane were synthesized from acetic acid-1-<sup>14</sup>C in 4 steps and from <sup>14</sup>C-formaldehyde in 1 step respectively. The radiochemical yeild for the ring labeling was 28.1%; for the side-chain labeling was 18.5%.展开更多
基金Science Foundation of Shanghai Higher Education (Grant No.97A49)
文摘Lipid peroxide (LPO) plays pivotal roles in the process and development of many diseases. In this work, we studied the inhibitory effect of probimane (Pro), a Chinese anticancer agent, on erythrocyte LPO and the interaction of Pro with sialic acids (sia). Malondialdehyde (MDA) of erythrocytes activated by hydrogen peroxide was measured. Pro was found to inhibit the product of LPO induced by hydrogen peroxide in a non-enzyme system of both rabbit and human erythrocytes in the absence of doxorubicin. Sia were found to enhance LPO production and the activity of N-glycolylneuraminic acid (NeuGc) was about 5 times higher than that of N-acetylneuraminic acid (5AcNeu) at equivalent concentrations. Pro inhibited the increased LPO production induced by sia and the activity of Pro against LPO with 5AcNeu was almost twofold higher than that of Pro alone. It suggests that Pro be an inhibitor of LPO (free radicals) and as a functional modulator of sia in body.
文摘To clarify the possible mechanisms of α anordin and probimane on calmodulin Ca^(++)-Mg^(++)-ATPase system, enzyme dynamic study was carried out by determining three dynamic parameters [the substrate concentration(ATP) response curve, dose(inhibitors) response curve and time response curve]. Our data have shown that the inhibitory rates of α anordrin and probimane are unrelated to substrate(APT) concentrations, but related to calmodulin concentrations. The inhibition of α anordrin and probimane is very quick that is completed within 1 to 5 min and can maintain more than 1 hr in the same inhibitory rates. So it is possible that α anordrin and probimane are calmodulin competitors with calmodulin like binding whose actions can occur by affecting the reaction balance of substrate and product on target enzymes of calmodulin( Ca^(++)-Mg^(++)-ATPase).
文摘To investigate the influence of probimane on the lipoperoxidation of human red cells in vitro. Malondialdehyde (MDA) of human red cells induced by hydrogen peroxide was assayed by means of colorimetry. It was shown that probimane ( > 2 μM ) could inhibit the lipoperoxidation without adriamycin. The inhibitory rates of probimane were 9.3 % ( 2 μM ) and 35.3 % ( 10 μM ) respectively ( P< 0.05). Probimane ( 2 μM ) inhibited lipoperoxidation in the presence of sialic acid ( 0.4 μM ) ( inhibitory rate 17.8 % ) was approximately two fold higher than those without sialic acid ( inhibitory rate 9.3 % ). So probimane may inhibit tumor growth through affecting lipoperoxidations and exhibit anticancer effects via sialic acids.
文摘The ring-and side-chain-<sup>14</sup>C-labeled probimane, 1,2-bis （4-morpholinomethy1-3,5-dioxopiperazin-1-yl） propane were synthesized from acetic acid-1-<sup>14</sup>C in 4 steps and from <sup>14</sup>C-formaldehyde in 1 step respectively. The radiochemical yeild for the ring labeling was 28.1%; for the side-chain labeling was 18.5%.
