Introduction: Due to the emergence of resistance to antimalarial drugs as well as the lack of vaccination for malaria, there is an urgent demand for the development of new antimalarial alternatives. Recently, our research group developed a new set of 3-alkylpyridine marine alkaloid analogs, of which a compound known as compound 5 was found to be inactive against Plasmodium falciparum.Methods: Herein, we report a successful halogenation strategy to improve the antiplasmodial activity of compound 5 through the replacement of a hydroxyl group by chlorine (compound 6) and fluorine (compound 7) atoms. Results: Compounds 6 and 7 showed improved antiplasmodial activities (IC₅₀ = 7.2 and 8.3 µM, respectively) 20 times higher than that of their precursor, compound 5 (IC₅₀ = 210.7 µM). Ultraviolet-visible titration experiments demonstrated that halogenation of compound 5 did not alter its ability to bind its target, hematin. Conclusion: Halogenation can enhance the antiplasmodial activity of a compound without altering its mechanism of action.