[Structure-activity-relationship study of the new anticancer drug lycobetaine (AT-1840)]

Lycobetaine (AT-1840), developed by our institute, is a new chemotherapeutic agent with relatively high percentage of remission on the treatment of ovary cancer and stomach cancer; no remarkable changes in blood picture, EKG and GPT, were observed. Early examination of the structure activity relationship of lycobetaine gave the following results: 1. A potential betaine and a methylenedioxy group in this compound may be critical for exhibiting antitumor activity; 2. Fission of the five membered ring of lycobetaine will not affect its antitumor activity. In order to see whether the distance between the phenolic oxygen and quaternary nitrogen affects its antitumor activity, compounds 7a-c, 8a-b were synthesized and screened against tumor in mice bearing EAC Preliminary experimental results showed that among the open ring analogs of lycobetaine, 7a, 7b and 8d possessed marked antitumor activity and 7c did not. The results indicate that changes in the distance of the betaine in lycobetaine obviously influence its antitumor activity.