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体外条件下吩噻嗪类衍生物 (PTZs)逆转多药耐药 (MDR)活性的实验结果表明 ,2位取代各种基团逆转MDR作用强度依次为 :COC3 H7>CF3 >COCH3 >H。边链哌嗪环 4’位取代基作用强度为 :CH3 >COOC2 H5>C2 H4OH。选出代表性化合物测定对鼠脑蛋白激酶C(PKC)的抑制活性 ,进行PTZs抑制PKC活性的初步三维构效关系研究 ,利用计算化学和分子图形学手段探讨PKC抑制剂与PKC蛋白分子间可能的相互作用模式。本研究为进一步探索PTZs、PKC和MDR三者间的内在机制和设计有效PKC抑制剂或多药耐药逆转剂提供了新的途径
The experimental results of reversing multidrug resistance (MDR) activity of phenothiazine derivatives (PTZs) in vitro showed that the intensity of reversing MDR by 2-position substituted groups was: COC3 H7> CF3> COCH3> H. The intensity of 4’-substituent on the piperazine ring of side chain is: CH3> COOC2 H5> C2 H4OH. Representative compounds were selected to determine inhibitory activity on murine brain protein kinase C (PKC), and to study the preliminary three-dimensional structure-activity relationship of PTZs inhibiting PKC activity. The computational chemistry and molecular profiling methods were used to explore the possible relationship between PKC inhibitors and PKC protein molecules Interaction model. This study provides a new approach to further explore the intrinsic mechanisms of PTZs, PKC and MDR and to design effective PKC inhibitors or multidrug resistance reversal agents