The lab made an effort to prepare some biological active cantharidinimines by heating the reactant 1 and 2a-g, 5h-i and 7j-r amines to suitable temperature with ethanol to provide 18 N-thiazolyl-, sulfanyl-, aminopyridyl-, bromopyridyl-, alkylpyridyl-and hydroxypyridylcantharidinimines 3a-g, 4a-c, 6h-i and 8j-r in yield of 4-77% (Chart 1). These cantharidinimine derivatives were tested for their capabilities to suppress growth of the human carcinoma cell lines, HL-60, MCF7, Neuro-2a and A549, because the incidence rate is more prominent in Asian countries than western countries. Compounds 3c-d and 6h-i were found to have some antitumor activity in HL-60 but less activity in MCF cell and compounds 8j-l displayed some inhibition effects to A549 cell line, but less effect to Neuro-2a cell line. Compounds 8m-r had no cytotoxic effect against both cell lines. The cytotoxic effects of these cantharidinimine compounds seemed to be better than the cantharidinimide compounds which we had mentioned several years ago.Key words cantharidin; N-azayl-thiadiazolylcantharidinimine; cytotoxicity; sulfanyl-thiadiazolylcantharidinimine; thiazolyl-thiadiazolylcantharidinimine Cantharidin 1 is found in Mylabris caraganae and various other insects and shows extremely high vesicant potency and toxic properties.1-4) Recent reports have indicated that the action of cantharidin in mice is associated with binding to phosphorylase 2A in liver cytosol and inhibition of its phosphorylase phosphastase activity. [5][6][7][8][9] In our previous studies, 10) increasing the solubility of the title compounds decreased the toxicity while maintaining the biological activities. N-Thiazolyl, sulfanylcantharidinimides with a better solubility showed high cytotoxicity against human carcinoma cell lines. The present study shows that characters of amine basicity and the chosen temperature are crucial. Furthermore the characters of the groups and their position on the aromatic or azalyl ring also influence yields. In order to obtain novel types of related imines and study the scope of these synthetic reactions, the same technique was applied to the reaction of compounds 1 with thiazolyl, thiadiazolyl, sulfanyl, or azalylamines in high-pressure tube with dry ethanol and heated to ca. 140°C. This temperature and reaction time influence the product yields. The method might give good yields after evaporated and recryatallization in methanol (Table 1). In our previous research, 11) we synthesized many cantharidinimide derivatives by modification with aliphatic, azalyl, thiazolyl, thiadiazolyl and pyridyl groups. Those compounds exhibited a certain degree of cytotoxic activity on HL-60, Hep3B and HepG2, [3][4][5] NUGC (Human Gastric carcinoma cells), HONZ-1 (Human Nasopharyngeal carcino cells) [11][12][13][14][15][16] . All of these compounds contained an imide group. Thus, we use this feature to synthesize different imine derivatives to study effects of antitumor therapy and cytotoxicity as carcinoma cells inhibitors and therapy sources. Results and DiscussionW...

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