Introduction: The objective of this study is to resolve the limitations of Morin, which is a natural flavonol that has various properties like antioxidant, anti-inflammatory, and anticancer. Morin's therapeutic application is limited due to factors such as poor aqueous sol-ubility, metabolic instability, and low bioavailability. The main objective of this study was to design and synthesize various semi-synthetic Morin derivatives by substituting the ortho po-sition with nitro, chloro, sulphur, and bromo groups to enhance their pharmacological activity and to assess their potential as antitumor agents against both breast and liver cancer. Methods: Novel substitution of Morin derivatives at the ortho position was synthesized by chemical substitution with groups like nitro, chloro, sulphur, and bromine. The cytotoxic po-tential of the synthesized derivatives was assessed in vitro against MCF7 (breast adenocarci-noma) and HepG2 (hepatocellular carcinoma) cell lines by the MTT method. In silico molec-ular docking studies were carried out with the help of the Epidermal Growth Factor Receptor (EGFR, PDB ID: 1M17) as a target to assess the binding affinities and potential EGFR-inhib-itory activity. Results: Nitro (MNI) and halogenated compounds like chloro, bromine (MBr) derivatives showed higher cytotoxicity, in which MNI demonstrated minimal toxicity toward HepG2 cells (CTC₅₀: 1111.97 μg/mL) but strong antiproliferative activity against MCF7 cells (CTC₅₀: 545.88 μg/mL). MBr exhibited moderate cytotoxicity against HepG2 cells (CTC₅₀: 969.82 μg/mL) and marked inhibitory effects on MCF7 cells (CTC₅₀: 612.70 μg/mL). Docking studies of these synthesized derivatives showed binding to EGFR and support receptor-medi-ated anticancer effects. Discussion: The results showed that ortho-substitution significantly increases the anticancer potential of Morin, with nitro- and halogen-substitutions boosting its cytotoxic activity. In the differential cytotoxicity profiles, specifically the low hepatic toxicity of MNI alongside its high potential in breast cancer cells. On the other hand, MBR derivatives showed moderate cytotoxicity against both hepatic and breast cancer cells. Conclusion: These studies concluded that Ortho-substituted Morin derivatives, especially the MNI derivative, are promising derivatives for breast cancer therapy due to their increased an-tiproliferative activity and lesser hepatotoxicity. Secondly, the MBR derivative showed mod-erate cytotoxicity for both breast and hepatic cell lines. These results indicate or suggest further mechanistic exploration and in vivo evaluation to validate their therapeutic potential.
Devi et al. (2026) studied this question.