In Vitro Study of Carbonyl Thiourea Derivatives’ Cytotoxicity on Human Corneal Epithelial Cells
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Abstract
Introduction: The global rise of Acanthamoeba keratitis infections has highlighted the shortcomings in the current treatments and prevention approaches for the disease. Therefore, this study is a continuation of our prior work and is intended to investigate the possible adverse effects of using carbonyl thiourea derivatives as alternative ocular drugs for amoebic keratitis on non-targeted human corneal epithelial cells (HCEC) in vitro. Methods: The efficacy and safety profiles of two carbonyl thiourea derivatives, 2-(3-benzoylthioureido)-3-mercaptopropanoic acid (M1) and 2-(3-benzoylthioureido-4-(methylthio)butanoic acid (M2), were tested on HCEC lines using the cytotoxicity assay and microscopic analysis. Results and Discussion: The carbonyl thiourea compounds were found to be non-toxic on HCEC with IC50 of 37.73 µg.mL-1 and 30.68 µg.mL-1 on M1 and M2, respectively. These compounds have selectivity indices (SI) of 14.74 (M1) and 11.38 (M2), indicating moderate selectivity for the targeted Acanthamoeba cells. HCEC-treated cells continued to proliferate in a time-dependent manner without significantly altering the cell population by retaining 90% viability. However, the microscopic examination revealed that HCECs were poorly differentiated and disintegrated, with irregular forms after the compound treatment, as opposed to their original hexagonal morphology of the healthy viable cells. The AO/PI staining indicated that the thiourea compounds impaired HCEC membrane integrity. Conclusions: This study's findings are critical in providing relevant information on carbonyl thiourea compounds if they were to be proposed as anti-amoebic agents in treating or preventing Acanthamoeba keratitis infection.
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