Design, synthesis, and preliminary anticancer evaluation of diphenylpropan-1-one derivatives: in vitro, in vivo and in silico studies
Abstract
Breast cancer is a leading cause of cancer-associated mortality and morbidity worldwide, and there is a continued need for structurally diverse anticancer agents with improved properties. The present study reports a series of diphenylpropan-1-one (DPP) derivatives (4a-4i), rationally designed around a chalcone framework and synthesized via a three-step reaction sequence. The physicochemical and spectral characterization of the synthesized derivatives was performed using spectral techniques. Their anticancer potential was evaluated through a preliminary in vitro cytotoxicity screening against the MCF-7 mammary cancer cell line, followed by an in vivo efficacy assessment using a DMBA-induced mammary cancer animal model. To explore a possible molecular target, in silico molecular docking was performed against the epidermal growth factor receptor (EGFR) tyrosine kinase domain as an exploratory computational analysis. Amongst the synthesized derivatives, compound 4h demonstrated the most potent cytotoxic effects (IC50 = 1.7 µg mL-1), comparable to the standard drug gefitinib (IC50 = 1.8 µg mL-1). The in vivo studies revealed a significant and dose-dependent decline in cellular proliferation and mammary gland tumor progression, along with histopathological abnormalities upon treatment with compound 4h. Interestingly, the quantitative gene expression analysis demonstrated a significant reduction in the DMBA-induced overexpression of BRCA1, BRCA2, and TP53 in the 4h-treated groups…
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Evidence Hub reads this as a simulation / modelling, done in animal and cell cultures (in vitro) and computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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