Synthesis, Characterization, DNA-Binding, and Anticancer Activity of 7-Methoxytetrahydropyrrolo[3,4-a]carbazole-1,3-diones Derivatives with Different Hydroxyl-Alkyl Side Chains

Objective: A series of new 7-methoxytetrahydropyrrolo[3,4-a]carbazole-1,3-diones derivatives (VIa–VIc) modified with hydroxyl-alkyl side chains have been synthesized and examined their biological activity. Based on their interaction with the DNA of the calf thymus (CT), the side chain effect on their ability to bind DNA was assessed and their cytotoxicity was assessed. Methods: The DNA-binding properties were studied by absorption spectroscopy, EB-DNA displacement, circular dichroism, viscosity, and thermal denaturation measurements. The anticancer activities of (VIa–VIc) were evaluated on different cell lines A549, HepG2, and K562. Results and Discussion: The experimental evidences indicated that compounds could interact with CT-DNA through intercalation into the base pairs of DNA. Compound (VIc) exhibited utmost DNA binding propensity and cytotoxicity compared to the compounds (VIa) and (VIb). The intrinsic binding constant values for compounds (VIa–VIc) were 1.0 × 10⁴, 0.372 × 10⁴, and 2.14 × 10⁵ M^–1 respectively, suggesting side chains plays a key role in DNA binding affinity. Conclusions: We talked about their structure and the relevance to bioactivity. Compound (VIc) has stronger cytotoxic action and more efficient DNA binding in similar experimental settings.