Abstract
Two N-substituted 2-methyl-4-/5-nitroimidazole derivatives (3 &4) have been synthesized by K2CO3 catalyzed reaction between 2-methyl-5-nitro-1H-imidazole (1) or metronidazole (2) and acrylonitrile. The derivates were obtained in good yields and characterized by IR spectroscopy, 1H-NMR spectroscopy, and ESI-MS mass spectrometry. Single-crystal X-ray structure analysis supported the formation of the derivatives, which were further complemented by DFT studies. The in-vitro anticancer activity against human colon cancer cell line (SW-480) has also been performed. To underpin the affinity of the reported derivatives towards nucleic acids, both in-vitro (ct-DNA binding studies) and in-silico (docking studies) techniques were employed. Despite their small sizeand the presence of pharmacologically active core, both 3 (IC50 > 160 μg/mL, Kb = 0.3 × 105 M−1, ΔG = −5.4 kcal/mol) and 4 (IC50 > 160 μg/mL, Kb = 3.0 × 105 M−1, ΔG = −5.6 kcal/mol) exhibited moderate anticancer activity and DNA affinity.
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•N-substituted 2-methyl-4-/5-nitroimidazole derivatives were synthesized.•Derivatives were characterized by different spectroscopic techniques.•The structure of hybrids was confirmed by X-ray crystallography.•DFT studies were conducted to further support the structure.•In vitro DNA binding, cell viability and docking studies were carried out.