Background: Acanthamoeba is an opportunistic pathogen widely spread in the environment.
Acanthamoeba causes excruciating keratitis which can lead to blindness. The lack of effective
drugs and its ability to form highly resistant cyst are one of the foremost limitations against
successful prognosis. Current treatment involves mixture of drugs at high doses but still recurrence
of infection can occur due to ineffectiveness of drugs against the cyst form. Pyridine and its natural
and synthetic derivatives are potential chemotherapeutic agents due to their diverse biological activities.
Objective: To study the antiamoebic effects of four novel synthetic dihydropyridine (DHP) compounds
against Acanthamoeba castellanii belonging to the T4 genotype. Furthermore, to evaluate
their activity against amoeba-mediated host cells cytopathogenicity as well as their cytotoxicity
against human cells.
Methods: Dihydropyridines were synthesized by cyclic dimerization of alkylidene malononitrile
derivatives. Four analogues of functionally diverse DHPs were tested against Acanthamoeba
castellanii by using amoebicidal, encystation and excystation assays. Moreover, Lactate dehydrogenase
assays were carried out to study cytopathogenicity and cytotoxicity against human cells.
Results: These compounds showed significant amoebicidal and cysticidal effects at 50 μM concentration,
whereas, two of the DHP derivatives also significantly reduced Acanthamoebamediated
host cell cytotoxicity. Moreover, these DHPs were found to have low cytotoxicity
against human cells suggesting a good safety profile.
Conclusion: The results suggest that DHPs have potential against Acanthamoeba especially
against the more resistant cyst stage and can be assessed further for drug development.