In contrast, conjugate 2 (containing a disulfide bridge) showed preferential toxicity to HT-1080 cells in the cytostatic experiments, resulting in the highest selectivity. The antitumor effect of 2 increased in time (72 h treatment), but its selectivity decreased significantly. In comparison to conjugates 3 (thioether linkage) and 5 (amide bond), both containing free Lys in the cycle, conjugate 5 had slightly better activity against HT-1080 cells. However, the selectivity of conjugate 5 to CD13 receptors (as judged by the relative toxicity against the two cell lines) was not significant after 6 h treatment, whereas it was significantly more toxic to HT-1080 cells in the 72 h experiment. This can also be explained by its higher chemostability that results in longer exposure the cells to the unmodified NGR peptide-drug conjugate. In contrast, their analogs in which the drug molecule is connected to the side chain of Lys in the cycle (conjugates 4 and 6) were more specific but less toxic, especially in the cytotoxicity experiments. Interestingly, there was no correlation between the specificity and the chemostability of the conjugates.

In contrast, conjugate 2 (containing a disulfide bridge) showed preferential toxicity to HT-1080 cells in the cytostatic experiments, resulting in the highest selectivity. The antitumor effect of 2 increased in time (72 h treatment), but its selectivity decreased significantly. In comparison to conjugates 3 (thioether linkage) and 5 (amide bond), both containing free Lys in the cycle, conjugate 5 had slightly better activity against HT-1080 cells. However, the selectivity of conjugate 5 to CD13 receptors (as judged by the relative toxicity against the two cell lines) was not significant after 6 h treatment, whereas it was significantly more toxic to HT-1080 cells in the 72 h experiment. This can also be explained by its higher chemostability that results in longer exposure the cells to the unmodified NGR peptide-drug conjugate. In contrast, their analogs in which the drug molecule is connected to the side chain of Lys in the cycle (conjugates 4 and 6) were more specific but less toxic, especially in the cytotoxicity experiments. Interestingly, there was no correlation between the specificity and the chemostability of the conjugates.

In contrast, conjugate 2 (containing a disulfide bridge) showed preferential toxicity to HT-1080 cells in the cytostatic experiments, resulting in the highest selectivity. The antitumor effect of 2 increased in time (72 h treatment), but its selectivity decreased significantly. In comparison to conjugates 3 (thioether linkage) and 5 (amide bond), both containing free Lys in the cycle, conjugate 5 had slightly better activity against HT-1080 cells. However, the selectivity of conjugate 5 to CD13 receptors (as judged by the relative toxicity against the two cell lines) was not significant after 6 h treatment, whereas it was significantly more toxic to HT-1080 cells in the 72 h experiment. This can also be explained by its higher chemostability that results in longer exposure the cells to the unmodified NGR peptide-drug conjugate. In contrast, their analogs in which the drug molecule is connected to the side chain of Lys in the cycle (conjugates 4 and 6) were more specific but less toxic, especially in the cytotoxicity experiments. Interestingly, there was no correlation between the specificity and the chemostability of the conjugates.

In contrast, conjugate 2 (containing a disulfide bridge) showed preferential toxicity to HT-1080 cells in the cytostatic experiments, resulting in the highest selectivity. The antitumor effect of 2 increased in time (72 h treatment), but its selectivity decreased significantly. In comparison to conjugates 3 (thioether linkage) and 5 (amide bond), both containing free Lys in the cycle, conjugate 5 had slightly better activity against HT-1080 cells. However, the selectivity of conjugate 5 to CD13 receptors (as judged by the relative toxicity against the two cell lines) was not significant after 6 h treatment, whereas it was significantly more toxic to HT-1080 cells in the 72 h experiment. This can also be explained by its higher chemostability that results in longer exposure the cells to the unmodified NGR peptide-drug conjugate. In contrast, their analogs in which the drug molecule is connected to the side chain of Lys in the cycle (conjugates 4 and 6) were more specific but less toxic, especially in the cytotoxicity experiments. Interestingly, there was no correlation between the specificity and the chemostability of the conjugates.