Bhushana Rao K S, Collard M P, Trouet A
Anticancer Res. 1985 Jul-Aug;5(4):379-86.
Vinblastine-23-oyl amino acid derivatives and the analog deoxy vinblastine derivative were synthesized by linking amino acid carbocyclic esters to the vinca-23-oyl moiety, through an amide linkage. Their experimental chemotherapeutic activities on P388, L1210 leukemias and 6C3HED lymphosarcoma in mice were evaluated in comparison to those of the parent alkaloids vinblastine, vincristine, and the semi-synthetic derivative vindesine. Further, their toxicities and plasmatic clearance are given. We have developed a method for conjugating vinca alkaloid to bovine serum albumin through a covalent and reversible linkage. The chemotherapeutic activity of this conjugate on P388 leukemia was assessed. This conjugate was found stable in blood and serum up to 48 hours. Lysosomal hydrolases liberate about 50 per cent of the tritiated drug after 48 hours.
通过酰胺键将氨基酸碳环酯连接到长春花-23-酰基部分，合成了长春碱-23-酰基氨基酸衍生物及其类似物脱氧长春碱衍生物。与母体生物碱长春碱、长春新碱和半合成衍生物长春地辛相比，评估了它们对小鼠P388、L1210白血病和6C3HED淋巴肉瘤的实验化疗活性。此外，还给出了它们的毒性和血浆清除率。我们开发了一种通过共价且可逆的连接将长春花生物碱与牛血清白蛋白偶联的方法。评估了该偶联物对P388白血病的化疗活性。发现该偶联物在血液和血清中长达48小时都是稳定的。48小时后，溶酶体水解酶释放出约50%的氚标记药物。
