ETD

• anticancer drugs
• peptide drug conjugates
• peptide synthesis

The goal of this work is to synthesize Peptide Drug conjugates (PDC) derived from the IndoCoquine drug. IndoCoquine itself has demonstrated potent cytotoxic activity against nine human cancer cell lines (HCT116, U87-MG, A549, MDA-MB231, MiaPACA2, HT1080, K562, K562R, HT29), attributed to its ability to inhibit tubulin polymerization and to induce mitochondrial dysfunction.
However, the excessive cytotoxicity of IndoCoquine limits its direct therapeutic use. To address this issue, this project aims to conjugate IndoCoquine to a peptide moiety designed to reduce its systemic toxicity while maintaining strong anticancer activity.
Three different IndoCoquine analogous were employed, differing only in the functional group used for peptide conjugation via a linker: an alcohol in IndoCoquine I, a methyl amine in the IndoCoquine II and a primary amine in the IndoCoquine III.
The resulting peptide-Indocoquine conjugates were synthesized and evaluated for their biological activity against three human cell lines: U87-MG (glioblastoma cells); RPE1 (normal retinal cells); MDA-MB231 (triple-negative breast cancer cells).
This study establishes a promising strategy for modulating IndoCoquine’s cytotoxic profile through peptide conjugation. The work will be further pursued in the framework of a Ph.D. project focused on optimizing the pharmacological properties of IndoCoquine-based PDCs. The results obtained will form the basis of a forthcoming patent application and subsequent scientific publication.