Abstract
Background: Phenolic Mannich bases derived from hydroxychalcones show remarkable cytotoxic potencies towards cancer cell lines. However, the exact mechanism of action is still partially uncleared. Objective: Interaction of two hydroxychalcones and their Mannich derivatives with calf thymus DNA (ctDNA) has been investigated. Methods: Thin-layer chromatography and UV-Vis spectroscopic method were used for studying the interaction. The binding constant has been determined by UV-Vis spectrophotometric titration. The DNA cleavage activity of the compounds was studied by agarose gel electrophoresis. Results: Interaction of the compounds with ctDNA exhibited relatively high intrinsic binding constant (4-5x104 M-1). The results indicate existence of weak, non-covalent interactions between the investigated derivatives with ctDNA. Some compounds showed a slight DNA cleavage activity with pBR322. Conclusion: The obtained results provide additional knowledge on the previously documented cytotoxicity against tumor cell lines of the hydroxychalcones and their Mannich-derivatives.
Highlights
Chalcones (1,3-diphenyl-prop-2-en-1-ones), are intermediary compounds of the biosynthetic pathway of a very large and widespread group of plant constituents, known collectively as flavonoids [1]
As a continuation of the previous works [32], here we report on synthesis and DNA binding properties of two 4'hydroxychalcones (1A and 2A) and their Mannich derivatives (Fig. 1 (1B and 2B))
For better understanding the molecular mechanism of cytotoxic effects of 4'hydroxychalcones and their Mannich analogs, here, we report results of thin-layer chromatographic and UV-Vis studies on the interaction of two 4'-hydroxychalcones (1A, 2A) and their Mannich derivatives (Fig. 1 (1B, 2B)) with calf thymus DNA
Summary
Chalcones (1,3-diphenyl-prop-2-en-1-ones), are intermediary compounds of the biosynthetic pathway of a very large and widespread group of plant constituents, known collectively as flavonoids [1]. It was concluded that biological activity, including the cytotoxic effect of chalcones and their some cyclic derivatives, might be partially a consequence of non-covalent interaction between the compounds and cellular macromolecules (proteins, DNA) [8 - 11]. Study on the Interaction of 4'-Hydroxychalcones and their Mannich Derivatives. The non-covalent binding of small molecules to DNA involves binding on the outside of the helix (external binding) through electrostatic interaction, intercalation between base pairs, and binding in the minor or major DNA grooves [13 - 15]. Phenolic Mannich bases derived from hydroxychalcones show remarkable cytotoxic potencies towards cancer cell lines. The exact mechanism of action is still partially uncleared
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