Aim: Cancer is a major health burden and a leading cause of death worldwide. We sought to discover potential anticancer molecules with novel scaffold for further development of more active agents to address the issue. Methodology: A series of beta-carboline-1-one hydantoins were designed according to a conformational restriction strategy, synthesized via a one-pot Knoevenagel condensation-intramolecular cyclization, and tested in cytotoxicity assays. Results: The study culminated in the identification of 6b and 6c, both of which were found to potently inhibit breast and lung cancer cell lines. Of particular interest was 6c, which was 83 times more potent an inhibitor than 5-fluorouracil in inhibiting MCF-7. Conclusion: This work establishes beta-carboline-1-one hydantoin as a promising scaffold in the investigation of anticancer agents.
