Vinblastin-23-oyl amino acid derivatives: chemistry, physicochemical data, toxicity, and antitumor activities against P388 and L1210 leukemias.

The dimeric alkaloids vinblastine (VLB) and vincristine (VCR) differ structurally only in the functional group on the dihydroindole nitrogen. The semisynthetic derivative vindesine (VDS) differs slightly from VLB by having an amide group instead of an ester group. However, these minor distinctions are responsible for profound differences in the oncolytic spectrum, potency, and toxicity of these compounds. Vinblastin-23-oyl amino acid derivatives were synthesized by linking amino acid carboxylic esters to the vinblastin-23-oyl moiety through an amide linkage. Studies were extended to explore the influence of the nature of the amino acid, the ester alkyl chain lengths, the stereoisomerism of the amino acid, or the reacetylation of the hydroxyl group (position O-4) of the vindoline moiety. The present study deals with the synthesis of 21 vinblastin-23-oyl amino acid derivatives, some of their physicochemical data, the acute toxicity in mice, and therapeutic activities of these derivatives against the P388 and L1210 leukemias in comparison with VDS, VBL, and VCR.

Vinblastine-C4 alkyl maleoyl and amino acid maleoyl derivatives: I. Chemistry and physicochemical data.

Vinblastine-C4 acyl derivatives were synthesized by linking alkyl maleoyl or amino acid maleoyl compounds through an ester linkage at the C4 position of the vindoline moiety of vinblastine. The condensation of the above mentioned compounds was performed by the mixed anhydride method. Their synthesis, yields and physiochemical data are reported.

Modification of Catharanthus roseus alkaloids: a lactone derived from 17-deacetylvinblastine.

A spirolactone with anti-tumor activity is formed during the reaction of paraformaldehyde with 17-deacetylvinblastine. The compound was identified by NMR techniques. The chemotherapeutic activity was assessed.