Synthesis of Prostate-Specific Membrane Antigen-Targeted Bimodal Conjugates of Cytotoxic Agents and Antiandrogens and Their Comparative Assessment with Monoconjugates

Abstract

Prostate cancer is the second most common cancer among men. We designed and synthesized new ligands targeting prostate-specific membrane antigen and suitable for bimodal conjugates with diagnostic and therapeutic agents. In vitro studies of the affinity of the synthesized compounds to the protein target have been carried out. Based on these ligands, a series of bimodal conjugates with a combination of different mitosis inhibitors and antiandrogenic drugs were synthesized. The cytotoxicity of the compounds obtained in vitro was investigated on three different cell lines. The efficacy of the two obtained conjugates was evaluated in vivo in xenograft models of prostate cancer. These compounds have been shown to be highly effective in inhibiting the growth of PSMA-expressing tumors.

Small Molecule‐Drug Conjugates: Opportunities for the Development of Targeted Anticancer Drugs

“…For example, in a recent study, a novel PSMA-targeting ligand suitable for bimodal coupling of diagnostic and therapeutic drugs was designed and synthesized, and the efficacy of these compounds on PSMA-expressing PCa cells was significantly increased. [40] Folate receptor α (FRα) is a folate-binding protein located on cell membrane that exhibits overexpression in several kinds of solid tumors including ovarian cancer, colon cancer, lung cancer, and breast cancer, [41] while in normal tissues or cells, FRα expression is minimal or absent. [42] Consequently, this receptor presents an appealing target for anticancer therapeutics.…”