Vinblastine-C4 alkyl maleoyl and amino acid maleoyl derivatives: III. Experimental antitumor activities of lactosaminated serum albumin conjugates

Vinblastine-C4 acyl derivatives were synthesized by linking alkyl maleoyl or amino acid maleoyl compounds through an ester linkage at C4 position of the Vindoline moiety of Vinblastine. To target these derivatives selectively to hepatoma, conjugates were prepared with a neoglycoprotein i.e. lactosaminated human albumin, as a specific carrier. The method of preparation of lactosaminated albumin and of coupling to Vinca alkaloid derivatives is described and the mechanism of addition of the protein to the derivative is discussed. The experimental antitumor activity of these conjugates has been screened against the experimental P-388 Leukemia. The activity of the best conjugate has been evaluated in several human tumor xenografts. Further, the therapeutic potential of this type of conjugate has been demonstrated in a model of hepatoma xenograft developed in our laboratory, the HepG2 carcinoma.