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Synthesis of three novel curcumin analog compounds and their activity tests against breast cancer based on in vitro, network pharmacology, and molecular docking assessments

Year: 2025

Type: article

Abstract: Breast cancer, the most common disease suffered by women, causes high mortality compared to other cancer types.This study aims to synthesize mono-carbonyl curcumin analogs and test their cytotoxic activity against four breast cancer cell lines, i.e., MCF-7, T47D, 4T1, and HER2, along with bioinformatics analysis, molecular docking, and pharmacokinetic profile prediction evaluation.Curcumin analogs were produced through aldol condensation, which reacting 3-bromo-4-methoxybenzaldehyde with various ketones to form N-benzyl-4-piperidone (A), 4-piperidone (B), and N-methyl-4-piperidone (C).Pharmacokinetic profiles showed that compounds A-C showed improved absorption, tissue distribution, retention, and toxicity profiles compared to curcumin.However, these compounds did not fully meet the Lipinski criteria, indicating limitations in oral bioavailability.Compound B exhibited the highest anticancer activity against T47D (IC 50 = 19.20 µg/ml) and HER2 cells (IC 50 = 30.70µg/ml).Compound A was found to the best against 4T1 cells (IC 50 = 174.05µg/ml) while compound C gave the best activity on MCF-7 cells (IC 50 = 110.91µg/ml).All compounds showed low efficacy, with a selectivity index value of lower than 3. Bioinformatics studies of the network pharmacology approach on cancer pathways showed that mitogen-activated protein kinase 8 protein became the main target of compound A while AKT1 protein was for compounds B and C. Further improvement in their activity and selectivity through targeted delivery systems and further molecular studies are recommended to enhance their therapeutic potential.

Source: Journal of Applied Pharmaceutical Science

DOI: 10.7324/japs.2025.231151