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The Croton cajucara (Euphorbiales, Euphorbiaceae) plant occurs widely in the Amazon region, where its leaves and stem bark are consumed by the population to treat several diseases. The secondary metabolite trans-dehydrocrotonin (DCTN) is mainly accountable for the biological activities of this plant. However, prolonged consumption is associated with hepatotoxic effects due to the furan ring present in the molecule. This group is responsible for toxicity reactions in other drugs. In this work, we inserted a COOH group into the molecule to prevent the formation of toxic intermediates. We assessed the cytotoxicity and genotoxicity of both molecules on HepG2 cells. Results showed that the new derivative (CCTN) is less cytotoxic and did not reduce cell viability at any concentration tested. Genotoxicity was also reduced as assessed by the comet and micronucleus assay. Therefore, the new derivative appears to be promising and additional tests should be performed to evaluate its therapeutic activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)