Research Information System
Fabad Journal of Pharmaceutical Sciences, vol.51, no.1, pp.163-174, 2026 (Scopus, TRDizin)
Cancer remains the second leading cause of death worldwide, accounting for approximately 20% of annual mortalities. Lung, breast, colon, and melanoma are among the most common cancer types, especially in developing countries. Kojic acid and its synthetic derivatives are known for their wide range of biological activities and applications in medicine, cosmetics, food, and agriculture. Mannich base derivatives of kojic acid have been previously reported to exhibit promising cytotoxic potential on various tumor cell lines. In this study, a series of kojic acid-based Mannich bases containing a piperidine ring were synthesized and evaluated for their anticancer effects on several cancer cell lines (SK-MEL, MCF-7, MDA-MB-231, A549, HeLa, Hep3B, HT-29, Neuro2A) and one healthy cell line (Vero). Among the synthesized compounds, Compound 4, containing a piperidinopiperidine moiety, demonstrated the highest and broadest cytotoxic activity, with IC50 values of 5.02 ± 0.09, 5.80 ± 0.06, and 5.92 ± 0.12 μM against MCF-7, Neuro2A, and SK-MEL cells, respectively. Flow cytometric analysis using the Annexin V method suggested that Compound 4 may induce apoptosis in a time-dependent manner, accompanied by G1 phase arrest in MCF-7 cells, although further molecular verification is required.