Cytogenotoxic Evaluation of Lercanidipine Hydrochloride in Human Lymphocytes Using Micronucleus, Chromosome Abnormalities, and Molecular Docking Assays.

This study evaluated the cytotoxic and genotoxic potential of lercanidipine hydrochloride (LHC) on human peripheral lymphocytes using in vitro and in silico approaches. The micronucleus (MN) test revealed a significant, dose-dependent increase in MNs, particularly after 24-h treatment (***p < 0.001), which suggests potential DNA damage. However, the chromosome aberration (CA) test did not yield statistically significant results, although a dose-related upward trend was observed. A substantial reduction in both the mitotic index (MI) and the nuclear division index (NDI) was observed at all concentrations (**p < 0.01, ***p < 0.001), indicating strong cytotoxic effects. In silico molecular docking analysis revealed that the ligand (LHC) binds to the minor groove of B-DNA with a binding energy of -7.7 kcal/mol, forming non-covalent interactions similar to those of the known minor groove binder Netropsin (-8.14 kcal/mol). By contrast, the positive control, mitomycin C (MMC), binds to the major groove via intercalation, forming covalent cross-links, with a binding energy of -5.45 kcal/mol. Although LHC's minor groove binding suggests a potential preference for AT-rich regions, its sequence specificity remains unconfirmed. Overall, these findings suggest that LHC primarily exhibits cytotoxic effects (e.g., inhibition of DNA replication or transcription), with only limited and preliminary evidence of genotoxic potential. Further studies are needed to elucidate the safety of LHC and its DNA interaction mechanisms.