2',4-Dihydroxychalcone is an orally active natural chalcone flavonoid. 2',4-Dihydroxychalcone restores intestinal barrier integrity by upregulating tight junction proteins, regulates intestinal flora balance and alleviates inflammation. 2',4-Dihydroxychalcone induces GPX4 degradation, ferroptosis and apoptosis, triggers cell cycle arrest, and exhibits broad anti-tumor activity. 2',4-Dihydroxychalcone also possesses antifungal activity, antileishmanial activity, and reduces the hemolytic effect and virulence of Vibrio vulnificus [1] [2] [3] [4] [5] [6].
In Vivo, 2',4-Dihydroxychalcone (10-30 mg/kg; i.g.; daily; 10 days) significantly alleviates DSS -induced acute ulcerative colitis in C57BL/6J mice by inhibiting NLRP3 inflammasome activation, restoring gut barrier integrity, and balancing gut microbiota, with no observed organ toxicity[1]. 2',4-Dihydroxychalcone (6.25-12.5 mg/kg; i.p.; repeated dosing schedule) significantly inhibits cholangiocarcinoma xenograft tumor growth with minimal organ toxicity[2]. 2',4-Dihydroxychalcone (15 mg/kg; injection; single dose) provides ~50% protection to Galleria mellonella larvae against Vibrio vulnificus infection[6].
In Vitro, 2',4-Dihydroxychalcone (1.25-40 μM; 1-2 h) selectively inhibits NLRP3 inflammasome activation in THP-1-derived macrophages and 774A.1 macrophages by blocking the cleavage of caspase-1 and Gasdermin D, and exhibits no cytotoxicity at concentrations up to 40 μM[1]. 2',4-Dihydroxychalcone (25 μM; 1 h) potently inhibits Nigericin -induced IL-1β secretion in THP-1-derived macrophages[1]. 2',4-Dihydroxychalcone (12.5-50 µM; 24-72 h) potently inhibits the proliferation of HuCCT1 and QBC939 cholangiocarcinoma cells in a concentration-dependent manner[2]. 2',4-Dihydroxychalcone (12.5-50 µM; 14 days) inhibits the colony-forming ability of HuCCT1 and QBC939 cholangiocarcinoma cells in a concentration-dependent manner[2]. 2',4-Dihydroxychalcone (25 µM; 24 h) inhibits the proliferation of HuCCT1 and QBC939 cholangiocarcinoma cells by reducing EdU incorporation[2]. 2',4-Dihydroxychalcone (12.5-50 µM; 48 h) inhibits horizontal and vertical migration of HuCCT1 and QBC939 cholangiocarcinoma cells in a concentration-dependent manner[2]. 2',4-Dihydroxychalcone (12.5-50 µM; 24 h) increases intracellular ROS levels in HuCCT1 and QBC939 cholangiocarcinoma cells in a concentration-dependent manner[2]. 2',4-Dihydroxychalcone (12.5-50 µM; 24 h) induces ferroptosis in HuCCT1 and QBC939 cholangiocarcinoma cells[2]. 2',4-Dihydroxychalcone (12.5-50 µM; 24 h) inhibits epithelial-mesenchymal transition in HuCCT1 and QBC939 cholangiocarcinoma cells, while downregulating the PI3K/AKT/mTOR signaling pathway and ferroptosis-related markers SLC7A11 and GPX4[2]. 2',4-Dihydroxychalcone (12.5-50 µM) downregulates the expression of ERO1A in HuCCT1 and QBC939 cholangiocarcinoma cells in a concentration-dependent manner[2]. 2',4-Dihydroxychalcone (0.06-256 μg/mL; 48 h) inhibits the metabolic activity and hyphal growth of Aspergillus fumigatus Af293, with an MIC50 ranging from 64 to 128 μg/mL, and significantly reduces hyphal growth at a concentration of 256 μg/mL[3]. 2',4-Dihydroxychalcone (8 μg/mL; 48 h) inhibits the radial growth of Aspergillus fumigatus Af293 by 20%, blocks its sporulation process, and reduces the expression levels of sporulation-related genes brlA, abaA and wetA by 3-5 folds[3]. 2',4-Dihydroxychalcone (8 μg/mL; 48 h) reduces the expression levels of calcineurin pathway genes cnaA and crzA in Aspergillus fumigatus Af293[3]. 2',4-Dihydroxychalcone (4-256 μg/mL; 48 h) enhances the antifungal activity of Itraconazole and Caspofungin against Aspergillus fumigatus Af293[3]. 2',4-Dihydroxychalcone (0.195-100.0 µg/mL; 72 h) potently inhibits the growth of Leishmania amazonensis promastigotes, with an IC50 of 0.4 μM, and this compound shows high selectivity for parasites over mammalian cells[4]. 2',4-Dihydroxychalcone (24 h) exhibits low cytotoxicity against mouse peritoneal macrophages, with a CC50 of 416.7 μM[4]. 2',4-Dihydroxychalcone (5-20 μg/mL; 48 h) induces morphological changes associated with apoptosis in human gastric cancer MGC-803 cells, with severe cell detachment and nuclear damage observed at the highest concentration[5]. 2',4-Dihydroxychalcone (5-20 μg/mL; 48 h) induces cell cycle arrest in human gastric cancer MGC-803 cells: it triggers S-phase arrest at 5 μg/mL, induces G2/M-phase arrest in a dose-dependent manner as the concentration increases to 10 μg/mL, while the G2/M-phase arrest effect attenuates at 20 μg/mL[5]. 2',4-Dihydroxychalcone (2.5-20 μg/mL; 48 h) increases the activity of caspase-3 in human gastric cancer MGC-803 cells in a dose-dependent manner[5]. 2',4-Dihydroxychalcone (5-20 μg/mL; 48 h) downregulates the expression of survivin mRNA in human gastric cancer MGC-803 cells in a dose-dependent manner[5]. 2',4-Dihydroxychalcone (0.2-5 μM; cultured to an OD600 of 1.8-2.0) potently reduces the transcription levels of HlyU-regulated toxin genes rtxA1 and vvhA in wild-type Vibrio vulnificus MO6-24/O, without altering the expression of hlyU or hns[6]. 2',4-Dihydroxychalcone (2-8 μM) inhibits the hemolytic activity of wild-type *Vibrio vulnificus* MO6-24/O in a concentration-dependent manner, and at the concentration of 8 μM, the hemolysis level decreases to a level comparable to that of the ΔhlyU mutant[6]. 2',4-Dihydroxychalcone exhibits low cytotoxicity against HeLa and HEK293 cells, with IC50 values of 100.3 μM and 60.0 μM, respectively, which are much higher than the maximum working concentration of 8 μM[6]. 2',4-Dihydroxychalcone (150-300 μM) inhibits the specific DNA-binding activity of purified wild-type Vibrio vulnificus HlyU protein with the PrtxA1 promoter, and prevents the formation of specific high-mobility DNA-protein complexes[6].
References:
[1]. Zhang G, et al. 2',4'-dihydroxychalcone alleviates inflammatory bowel disease by inhibiting NLRP3 inflammasome and modulating gut microbiota. Frontiers in immunology. 2026;17:1751218.
[2]. Wang T, et al. 2',4'-dihydroxychalcone induces ferroptosis through ERO1A/GPX4 regulatory axis in cholangiocarcinoma. Phytomedicine: international journal of phytotherapy and phytopharmacology. 2025 Nov;147:157192.
[3]. Seo YH, et al. In Vitro Antifungal Activity and Mode of Action of 2',4'-Dihydroxychalcone against Aspergillus fumigatus. Mycobiology. 2015 Jun;43(2):150-6.
[4]. Passalacqua TG, et al. The 2',4'-dihydroxychalcone could be explored to develop new inhibitors against the glycerol-3-phosphate dehydrogenase from Leishmania species. Bioorganic & medicinal chemistry letters. 2015 Sep 01;25(17):3564-8.
[5]. Lou C, et al. 2',4'-Dihydroxychalcone-induced apoptosis of human gastric cancer MGC-803 cells via down-regulation of survivin mRNA. Toxicology in vitro: an international journal published in association with BIBRA. 2010 Aug;24(5):1333-7.
[6]. Imdad S, et al. Identification of 2',4'-Dihydroxychalcone as an Antivirulence Agent Targeting HlyU, a Master Virulence Regulator in Vibrio vulnificus. Molecules. 2018 Jun 20;23(6):1492.
In Vivo, 2',4-Dihydroxychalcone (10-30 mg/kg; i.g.; daily; 10 days) significantly alleviates DSS -induced acute ulcerative colitis in C57BL/6J mice by inhibiting NLRP3 inflammasome activation, restoring gut barrier integrity, and balancing gut microbiota, with no observed organ toxicity[1]. 2',4-Dihydroxychalcone (6.25-12.5 mg/kg; i.p.; repeated dosing schedule) significantly inhibits cholangiocarcinoma xenograft tumor growth with minimal organ toxicity[2]. 2',4-Dihydroxychalcone (15 mg/kg; injection; single dose) provides ~50% protection to Galleria mellonella larvae against Vibrio vulnificus infection[6].
In Vitro, 2',4-Dihydroxychalcone (1.25-40 μM; 1-2 h) selectively inhibits NLRP3 inflammasome activation in THP-1-derived macrophages and 774A.1 macrophages by blocking the cleavage of caspase-1 and Gasdermin D, and exhibits no cytotoxicity at concentrations up to 40 μM[1]. 2',4-Dihydroxychalcone (25 μM; 1 h) potently inhibits Nigericin -induced IL-1β secretion in THP-1-derived macrophages[1]. 2',4-Dihydroxychalcone (12.5-50 µM; 24-72 h) potently inhibits the proliferation of HuCCT1 and QBC939 cholangiocarcinoma cells in a concentration-dependent manner[2]. 2',4-Dihydroxychalcone (12.5-50 µM; 14 days) inhibits the colony-forming ability of HuCCT1 and QBC939 cholangiocarcinoma cells in a concentration-dependent manner[2]. 2',4-Dihydroxychalcone (25 µM; 24 h) inhibits the proliferation of HuCCT1 and QBC939 cholangiocarcinoma cells by reducing EdU incorporation[2]. 2',4-Dihydroxychalcone (12.5-50 µM; 48 h) inhibits horizontal and vertical migration of HuCCT1 and QBC939 cholangiocarcinoma cells in a concentration-dependent manner[2]. 2',4-Dihydroxychalcone (12.5-50 µM; 24 h) increases intracellular ROS levels in HuCCT1 and QBC939 cholangiocarcinoma cells in a concentration-dependent manner[2]. 2',4-Dihydroxychalcone (12.5-50 µM; 24 h) induces ferroptosis in HuCCT1 and QBC939 cholangiocarcinoma cells[2]. 2',4-Dihydroxychalcone (12.5-50 µM; 24 h) inhibits epithelial-mesenchymal transition in HuCCT1 and QBC939 cholangiocarcinoma cells, while downregulating the PI3K/AKT/mTOR signaling pathway and ferroptosis-related markers SLC7A11 and GPX4[2]. 2',4-Dihydroxychalcone (12.5-50 µM) downregulates the expression of ERO1A in HuCCT1 and QBC939 cholangiocarcinoma cells in a concentration-dependent manner[2]. 2',4-Dihydroxychalcone (0.06-256 μg/mL; 48 h) inhibits the metabolic activity and hyphal growth of Aspergillus fumigatus Af293, with an MIC50 ranging from 64 to 128 μg/mL, and significantly reduces hyphal growth at a concentration of 256 μg/mL[3]. 2',4-Dihydroxychalcone (8 μg/mL; 48 h) inhibits the radial growth of Aspergillus fumigatus Af293 by 20%, blocks its sporulation process, and reduces the expression levels of sporulation-related genes brlA, abaA and wetA by 3-5 folds[3]. 2',4-Dihydroxychalcone (8 μg/mL; 48 h) reduces the expression levels of calcineurin pathway genes cnaA and crzA in Aspergillus fumigatus Af293[3]. 2',4-Dihydroxychalcone (4-256 μg/mL; 48 h) enhances the antifungal activity of Itraconazole and Caspofungin against Aspergillus fumigatus Af293[3]. 2',4-Dihydroxychalcone (0.195-100.0 µg/mL; 72 h) potently inhibits the growth of Leishmania amazonensis promastigotes, with an IC50 of 0.4 μM, and this compound shows high selectivity for parasites over mammalian cells[4]. 2',4-Dihydroxychalcone (24 h) exhibits low cytotoxicity against mouse peritoneal macrophages, with a CC50 of 416.7 μM[4]. 2',4-Dihydroxychalcone (5-20 μg/mL; 48 h) induces morphological changes associated with apoptosis in human gastric cancer MGC-803 cells, with severe cell detachment and nuclear damage observed at the highest concentration[5]. 2',4-Dihydroxychalcone (5-20 μg/mL; 48 h) induces cell cycle arrest in human gastric cancer MGC-803 cells: it triggers S-phase arrest at 5 μg/mL, induces G2/M-phase arrest in a dose-dependent manner as the concentration increases to 10 μg/mL, while the G2/M-phase arrest effect attenuates at 20 μg/mL[5]. 2',4-Dihydroxychalcone (2.5-20 μg/mL; 48 h) increases the activity of caspase-3 in human gastric cancer MGC-803 cells in a dose-dependent manner[5]. 2',4-Dihydroxychalcone (5-20 μg/mL; 48 h) downregulates the expression of survivin mRNA in human gastric cancer MGC-803 cells in a dose-dependent manner[5]. 2',4-Dihydroxychalcone (0.2-5 μM; cultured to an OD600 of 1.8-2.0) potently reduces the transcription levels of HlyU-regulated toxin genes rtxA1 and vvhA in wild-type Vibrio vulnificus MO6-24/O, without altering the expression of hlyU or hns[6]. 2',4-Dihydroxychalcone (2-8 μM) inhibits the hemolytic activity of wild-type *Vibrio vulnificus* MO6-24/O in a concentration-dependent manner, and at the concentration of 8 μM, the hemolysis level decreases to a level comparable to that of the ΔhlyU mutant[6]. 2',4-Dihydroxychalcone exhibits low cytotoxicity against HeLa and HEK293 cells, with IC50 values of 100.3 μM and 60.0 μM, respectively, which are much higher than the maximum working concentration of 8 μM[6]. 2',4-Dihydroxychalcone (150-300 μM) inhibits the specific DNA-binding activity of purified wild-type Vibrio vulnificus HlyU protein with the PrtxA1 promoter, and prevents the formation of specific high-mobility DNA-protein complexes[6].
References:
[1]. Zhang G, et al. 2',4'-dihydroxychalcone alleviates inflammatory bowel disease by inhibiting NLRP3 inflammasome and modulating gut microbiota. Frontiers in immunology. 2026;17:1751218.
[2]. Wang T, et al. 2',4'-dihydroxychalcone induces ferroptosis through ERO1A/GPX4 regulatory axis in cholangiocarcinoma. Phytomedicine: international journal of phytotherapy and phytopharmacology. 2025 Nov;147:157192.
[3]. Seo YH, et al. In Vitro Antifungal Activity and Mode of Action of 2',4'-Dihydroxychalcone against Aspergillus fumigatus. Mycobiology. 2015 Jun;43(2):150-6.
[4]. Passalacqua TG, et al. The 2',4'-dihydroxychalcone could be explored to develop new inhibitors against the glycerol-3-phosphate dehydrogenase from Leishmania species. Bioorganic & medicinal chemistry letters. 2015 Sep 01;25(17):3564-8.
[5]. Lou C, et al. 2',4'-Dihydroxychalcone-induced apoptosis of human gastric cancer MGC-803 cells via down-regulation of survivin mRNA. Toxicology in vitro: an international journal published in association with BIBRA. 2010 Aug;24(5):1333-7.
[6]. Imdad S, et al. Identification of 2',4'-Dihydroxychalcone as an Antivirulence Agent Targeting HlyU, a Master Virulence Regulator in Vibrio vulnificus. Molecules. 2018 Jun 20;23(6):1492.