Synthesis, DNA-binding, molecular docking, and cytotoxic activity of a new 4-amino-N-(5-selenocyanatothiazol-2-yl) benzenesulfonamide

Triselenium dicyanide (TSD, 2) was combined with 4-amino-N-(thiazol-2-yl) benzenesulfonamide (3) in DMSO to form 4-amino-N-(5-selenocyanatothiazol-2-yl) benzenesulfonamide (4). Acetamide 5 was formed by acetylation of seleno derivative 4 with acetic anhydride. The absorption and fluorescence methods were used to monitor the interaction of compounds 3-5 with the double strain fish sperm deoxyribonucleic acid (dsFS-DNA), revealing a groove binding interaction with a binding constant in the order of 104 M-1. The measured Gibbs free energies, entropies, and enthalpy changes indicated that all interaction processes were spontaneous, with the hydrogen bonding and van der Waals interactions playing important participation for the binding of 3-5 with FS-DNA. Based on the molecular modeling results, the compound binds to the groove of B-DNA with a relative binding energy of-5.06 to-5.94 kcal mol-1. Biological investigations revealed that compound 4 was the most cytotoxic against Panc1 cells with IC50 value of 9.3 mu g/mL compared to Doxorubicin (IC50=3.16 mu g/mL). It induced apoptosis in Panc1 cells, increasing the death rate by 31.38-fold; it induced total apoptosis by 20.4% (8.2% for early apoptosis, 22.2 % for late apoptosis) compared to 0.65% in the untreated control group. Additionally, compound 4 and 5 exhibited remarkable antioxidant activity with a DPPH inhibition ratio of 71.6 and 56.6% compared to Trolox (96%) at the highest concentration of 100 mu M. The findings of this research offer additional useful insights regarding organoselenium compound-DNA interactions as promising cytotoxic agents through apoptosis.

Automated summary

In this study, the combination of Triselenium dicyanide with 4-amino-N-(thiazol-2-yl) benzenesulfonamide resulted in the synthesis of 4-amino-N-(5-selenocyanatothiazol-2-yl) benzenesulfonamide. The interaction between compounds 3-5 and dsFS-DNA was investigated, and groove binding with a binding constant of 104 M-1 was observed. Molecular modeling revealed that the compound binds to the groove of B-DNA with a relative binding energy of -5.06 to -5.94 kcal mol-1. Additionally, compound 4 exhibited strong cytotoxicity against Panc1 cells, inducing apoptosis and demonstrating significant antioxidant activity.