ArticleDaru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences2026
Novel 3,3'-diindolylmethane derivatives as multi-pathway modulators: targeting estrogen-dependent and independent breast cancer carcinogenesis.
Article in Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeBreast cancer remains a leading cause of cancer-related mortality among women, with prolonged exposure to endogenous estrogens recognized as a major risk factor. This study aimed to design, synthesize, and pharmacologically evaluate novel 3,3'-diindolylmethane (DIM) derivatives as multi-target modulators of estrogen-related pathways in breast cancer.
methodsA series of DIM derivatives was synthesized and structurally characterized. Their biological activities were assessed through aromatase (CYP19A1) and CYP1B1 inhibition assays, E-screen assay for estrogen receptor activity, cytotoxicity assays in breast cancer (MCF-7 BUS, MDA-MB-231) and normal breast epithelial (MCF-10 A) cells, and scratch assay for cell migration. Molecular docking and in silico ADME analyses were conducted to support experimental findings.
resultsThe derivatives demonstrated significant antiestrogenic activity by targeting multiple components of estrogen signaling. One compound exhibited potent aromatase inhibition (IC₅₀ = 0.79 µM), while two derivatives showed strong CYP1B1 inhibition (IC₅₀ = 0.37 µM and 0.71 µM). Selective cytotoxicity was observed in estrogen receptor-positive cells, with reduced effects on normal cells. Additionally, selected compounds significantly inhibited cell migration. Molecular modeling revealed favorable binding interactions within target enzymes, and ADME analysis indicated acceptable drug-like properties.
conclusionThese findings suggest that DIM derivatives act as selective, multi-target modulators of estrogen-related pathways and may serve as promising adjuvant candidates for hormone-dependent breast cancer therapy.
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