ロペラミドのピペリジン窒素原子上置換基の変換と抗腫瘍活性との相関

抄録

Opioid analgesics, like a morphine, are widely used for severe pain of cancer. Recently, treatment with high concentration of buprenorphine and loperamide, which are opioid analogs, has been reported to induce apoptosis of human carcinoma, such as human lung cancer derived A549 cells. Both the molecular mechanisms and the required chemical structures of opioids for antitumor activity have been still unclear. Loperamide consists of two moieties, the 4-arylpiperidine unit and the N-substituent unit on piperidine. In this work, loperamide analogs, in which the N-substituents on piperidine are converted to the phenylalkyl groups, have been synthesized and tested the antitumor activities against human colon tumor derived HCT-116 cells. The N-phenylnonyl analog showed most potent inhibition of the tumor cells viability.