Multifunctional N-substituted 2-pyridylbenzothiazole derivatives: singlet oxygen generation, protein binding, and photoactivated anticancer and antibacterial activities

Abstract

This study presents the optical characteristics, and biological characteristics of four N-substituted 2-pyridylbenzothiazole derivatives, namely 6-amino-5-(2-benzothiazolyl)-2-oxo-1-phenyl-1,2-dihydro-3-pyridinecarbonitrile (BTZ-Ph), 6-amino-5-(2-benzothiazolyl)-2-oxo-1-(4-chlorophenyl)-1,2-dihydro-3-pyridinecarbonitrile (BTZ-ClPh), 6-amino-5-(2-benzothiazolyl)-2-oxo-1-(4-methylphenyl)-1,2-dihydro-3-pyridinecarbonitrile (BTZ-MePh), and 6-amino-5-(2-benzothiazolyl)-2-oxo-1-(naphthalen-1-yl)-1,2-dihydro-3-pyridinecarbonitrile (BTZ-Nap). The steady-state absorption and emission properties of the examined compounds were assessed in acetonitrile solutions. The fluorescence quantum yields were determined to be 0.27 (BTZ-Ph), 0.24 (BTZ-ClPh), 0.28 (BTZ-MePh), and 0.25 (BTZ-Nap). The biological studies showed a significant interaction of the examined compounds with bovine serum albumin (BSA), where the binding constant (K), Stern–Volmer quenching constant (K_sv), and the number of binding sites were determined. Steady-state fluorescence and time-correlated single photon counting suggest a highly probable energy transfer pathway from the BSA singlet excited state to the examined compounds. The antibacterial activity was evaluated using disc diffusion and minimum inhibitory concentration (MIC) techniques under both dark and light conditions. The compounds exhibited significant antibacterial activity when subjected to blue illumination. The examined N-substituted 2-pyridylbenzothiazole derivatives exhibited markedly enhanced photo-cytotoxicity against human breast cancer MCF-7 (at IC₅₀ values of 69.54, 49.78, 9.86, and 16.54 µg mL⁻¹ for BTZ-Ph, BTZ-ClPh, BTZ-MePh, and BTZ-Nap, respectively) and human colorectal carcinoma HCT-116 cell lines (at IC₅₀ values of 47.65, 147.98, 56.98, and 22.32 µg mL⁻¹ for BTZ-Ph, BTZ-ClPh, BTZ-MePh, and BTZ-Nap, respectively) when subjected to blue light excitation at 450 nm. Molecular docking was employed to elucidate the interaction mechanism of the compounds with BSA, revealing that BTZ-Ph exhibited a higher binding energy. The determined BSA-binding constants correlated effectively with the antibacterial and cytotoxic outcomes, as well as the molecular docking data. Significantly, the compounds demonstrated encouraging singlet oxygen quantum yields in acetonitrile, ranging from 0.18 to 0.33 (detected via luminescence), suggesting their potential for cancer photodynamic therapy. These findings suggest the potential of these materials as a multifunctional platform for singlet oxygen generation, protein interaction, and photo-enhanced bioactivity.