Work

Synthesis of 1,2,3,4‐Tetrahydroisoquinoline‐3‐Carboxylic Acid‐Embedded Decapeptides: In Silico Studies and In Vitro Evaluation Against Breast Cancer

Year: 2025

Type: article

Abstract: Cancer is a leading cause of mortality worldwide, which has led to further research in developing more effective therapeutics. We synthesized amphipathic cationic peptides incorporating 1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid (Tic acid) into their backbones to explore their potential anticancer properties. The MCF‐7 cell line was selected to evaluate cell viability, inhibition percentage, and cytotoxic effects of the synthesized decapeptides. The results suggested DEC‐1 (IC 50 = 3.38 µM) to be the most potent candidate, showcasing antiproliferative activity similar to the standard drug tamoxifen (IC 50 = 2.68 µM). Structural characterization of the peptides confirmed the successful incorporation of Tic into the peptide backbones. The peptides were docked with xanthine oxidase (PDB ID: 2CKJ) and Nrf2 (Nuclear factor erythroid 2‐related factor 2) inhibitor protein Keap‐1 (PDB ID: 7Q6S), revealing strong binding interactions, particularly for DEC‐1, having a binding score of nearly −8.864 kcal/mol—which is stronger than its reference ligand with Keap‐1 protein—suggesting possible inhibitory roles in cancer cell proliferation and oxidative stress regulation. These promising findings indicate that the potent molecule DEC‐1 can be taken for further studies and might lead to a potential therapeutic agent for cancer treatment.

Source: ChemistryOpen

DOI: 10.1002/open.202500282