半合成三尖杉酯碱的抗肿瘤作用及毒性研究

Partial synthetic harringtonine was prepared as a mixture of two diastereoisomers ——harringtonine and epiharringtonine. Experimental chemotherapeutic studies'revealed that the partial synthetic harringtonine was as active as the natural harringtonine in rodent tumors (L615, L1210, and P388 leukemia, Lewis lung carcinoma, S180 and Walker256 careinosarcoma). Toxicity studies showed that the LD₅₀ of the synthetic mixture was twice as that of natural harringtonine. The biological activity of one of the diastereoisomers epiharringtonine was shown to be less than 1% of that of the other diastereoisomer——harringtonine. Epiharringtonine given intraperitoneally did not prolong the survival time of P388 leukemia mice. However, the effect of epiharringtonine in combination with harringtonine was higher than that of harringtonine alone.

STUDIES ON THE ANTINEOPLASTIC ACTION AND TOXICITY OF PARTIAL SYNTHETIC HARRINGTONINE

Partial synthetic harringtonine was prepared as a mixture of two diastereoisomers ——harringtonine and epiharringtonine. Experimental chemotherapeutic studies'revealed that the partial synthetic harringtonine was as active as the natural harringtonine in rodent tumors (L615, L1210, and P388 leukemia, Lewis lung carcinoma, S180 and Walker256 careinosarcoma). Toxicity studies showed that the LD₅₀ of the synthetic mixture was twice as that of natural harringtonine. The biological activity of one of the diastereoisomers epiharringtonine was shown to be less than 1% of that of the other diastereoisomer——harringtonine. Epiharringtonine given intraperitoneally did not prolong the survival time of P388 leukemia mice. However, the effect of epiharringtonine in combination with harringtonine was higher than that of harringtonine alone.