| Summary: | Incomptine A (<b>IA</b>) is a sesquiterpene lactone isolated from <i>Decachaeta incompta</i> that induces apoptosis, reactive oxygen species production, and a differential protein expression on the U-937 (diffuse histiocytic lymphoma) cell line. In this work, the antitumor potential of <b>IA</b> was investigated on Balb/c mice inoculated with U-937 cells and through the brine shrimp lethality (BSL) test. Furthermore, <b>IA</b> was subjected to molecular docking study using as targets proteins associated with processes of cancer as apoptosis, oxidative stress, and glycolytic metabolism. In addition to determining the potential toxicity of <b>IA</b> in human, its acute toxicity was performed in mice. Results reveals that <b>IA</b> showed high antilymphoma activity and BSL with an EC<sub>50</sub> of 2.4 mg/kg and LC<sub>50</sub> 16.7 µg/mL, respectively. The molecular docking study revealed that <b>IA</b> has strong interaction on all targets used. In the acute oral toxicity, <b>IA</b> had a LD<sub>50</sub> of 149 mg/kg. The results showed that the activities of <b>IA</b> including antilymphoma activity, BSL, acute toxicity, and in silico interactions were close to the methotrexate, an anticancer drug used as positive control. These findings suggest that <b>IA</b> may serve as a candidate for the development of a new drug to combat lymphoma.
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