Vinca-23-oyl amino acid derivatives: as new anticancer agents (review).

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.