Capsaicin (CAP) is the main compound responsible for the spicy flavor of Capsicum plants. However, its application can be inhibited due to its pungency and toxicity. This study aimed to evaluate and compare the cytotoxic effect of CAP and its analogs N-benzylbutanamide (AN1), N-(3-methoxybenzyl) butanamide (AN2), N-(4-hydroxy-3-methoxybenzyl) butanamide (AN3), N-(4-hydroxy-3-methoxybenzyl)
hexanamide (AN4) and N-(4-hydroxy-3-methoxybenzyl) tetradecanamide (
AN5) on the
hepatoma cells of Rattus norvegicus using the MTT test. The results showed cytotoxicity of CAP at concentrations of 100, 150, 175, and 200 μM (24 hours), AN1 at 150 and 175 μM (48 hours), AN2 at 50 μM (24 hours) and 10, 25, 50, and 75 μM (48 hours), AN4 at 175 μM (24 hours), and
AN5 at 50 μM (48 hours). Removing the
hydroxyl radical from the vanillyl group of
capsaicin, together with reducing the acyl chain to 3 carbons, which is the case of AN2, resulted in the best
biological activity. Increasing the
carbon chain in the acyl group of the
capsaicin molecule, which is the case of
AN5, also showed evident cytotoxic effects. The present study proves that the chemical modifications of
capsaicin changed its
biological activity.