Introduction:

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide in both men and women. Current therapeutic options rarely achieve complete remission, highlighting the urgent need for new treatments. The sigma-1 (σ₁) receptor has emerged as a promising target since it is overexpressed in several tumor types. Antagonists of this receptor have been shown to inhibit cell proliferation by inducing endoplasmic reticulum stress and promoting the generation of reactive oxygen species. Interestingly, although σ₁ receptors are also present in normal cells, their antagonists selectively trigger cytotoxic effects in cancer cells.

Methods:

In this study, we evaluated the cytotoxic activity of naphthoxyacetamide hydrochlorides through cell viability assays based on the metabolic reduction of MTT. Two compounds were tested: N-(2-morpholinoethyl)-2-(naphthalen-2-yloxy)acetamide (salt 1) and N-(2-(piperidin-1-yl)ethyl)-2-(naphthalen-2-yloxy)acetamide (salt 2). A549 lung adenocarcinoma cells were seeded at a density of 5000 cells/well in 96-well plates and exposed to different concentrations (0.1–3.16 μmol/mL) for 24 h. Absorbance was measured at 575 nm using a microplate reader.

Results:

Salt 2 exhibited a half-maximal inhibitory concentration (IC₅₀) of 0.381 μmol/mL, which was comparable to the reference drug cisplatin (0.358 μmol/mL). In contrast, salt 1 showed a higher IC₅₀ value of 1.419 μmol/mL, indicating lower potency.

Conclusions:

Both compounds demonstrated cytotoxic activity against A549 cells, with salt 2 displaying a stronger effect like cisplatin. These findings suggest that salt 2 could be considered a promising candidate for further development as an anticancer agent targeting NSCLC.