Synthetic Methodologies and Therapeutic Potential of Indole-3-Carbinol (I3C) and Its Derivatives

Indole-3-carbinol (I3C) is a natural product contained in vegetables belonging to the Brassicaceae family and has been studied in recent decades for its biological and pharmacological properties. Herein, we will analyze: (1) the biosynthetic processes and synthetic procedures through which I3C and its main derivatives have been obtained; (2) the characteristics that lead to believe that both I3C and its derivatives are responsible for several important activities—in particular, antitumor and antiviral, through insights concerning in vitro assays and in vivo tests; (3) the mechanisms of action of the most important compounds considered; (4) the potential social impact that the enhancement of the discussed molecules can have in the prevention and treatment of the pathologies’ examined field—first of all, those related to respiratory tract disorders and cancer.

• Publication year

  2023

• Venue

  Pharmaceuticals

• Publication date

  2023-02-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.3390/ph16020240PMID 37259386PMCID 9960368
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Friedel-Crafts arylation of aldehydes with indoles utilizing arylazo sulfones as the photoacid generator.

  2023influential reference
• Efficacy of antiviral therapies for COVID-19: a systematic review of randomized controlled trials

  2022cited by this paper
• Breakthrough infections with SARS-CoV-2 omicron despite mRNA vaccine booster dose

  2022cited by this paper
• The Anticancer Agent 3,3'-Diindolylmethane Inhibits Multispecies Biofilm Formation by Acne-Causing Bacteria and Candida albicans

  2022cited by this paper
• Elevated ubiquitination contributes to protective immunity against severe SARS‐CoV‐2 infection

  2022cited by this paper
• Ubiquitin variants potently inhibit SARS-CoV-2 PLpro and viral replication via a novel site distal to the protease active site

  2022cited by this paper
• Cruciferous vegetables as a treasure of functional foods bioactive compounds: Targeting p53 family in gastrointestinal tract and associated cancers

  2022cited by this paper
• Indole-3-Carbinol (I3C) Protects the Heart From Ischemia/Reperfusion Injury by Inhibiting Oxidative Stress, Inflammation, and Cellular Apoptosis in Mice

  2022cited by this paper
• SARS-CoV-2 Main Protease Drug Design, Assay Development, and Drug Resistance Studies

  2022cited by this paper
• Assessing vaccine effectiveness against severe COVID-19 disease caused by omicron variant. Report from a meeting of the World Health Organization

  2022cited by this paper
• Anti-breast cancer effects of phytochemicals: primary, secondary, and tertiary care

  2022cited by this paper
• Cruciferous Vegetables and Their Bioactive Metabolites: from Prevention to Novel Therapies of Colorectal Cancer

  2022influential reference
• Indole-3-carbinol in vitro antiviral activity against SARS-Cov-2 virus and in vivo toxicity

  2022cited by this paper
• Two Different Therapeutic Approaches for SARS-CoV-2 in hiPSCs-Derived Lung Organoids

  2022cited by this paper
• Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables

  2022influential reference
• The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood

  2021cited by this paper
• Indoles Derived From Glucobrassicin: Cancer Chemoprevention by Indole-3-Carbinol and 3,3'-Diindolylmethane

  2021influential reference
• Editorial: SARS-CoV-2 Vaccine Responses and Breakthrough COVID-19

  2021cited by this paper
• Biomedical application of Indole-3-carbinol: A mini-review

  2021cited by this paper
• Incidence of medically attended acute respiratory illnesses due to respiratory viruses across the life course during the 2018/19 influenza season

  2021cited by this paper
• Neuroprotective effects of indole-3-carbinol on the rotenone rat model of Parkinson's disease: Impact of the SIRT1-AMPK signaling pathway.

  2021cited by this paper
• Inhibition of HECT E3 ligases as potential therapy for COVID-19

  2021influential reference
• COVID-19 vaccines: effectiveness and number needed to treat – Authors' reply

  2021cited by this paper
• 3,3′-Diindolylmethane Exhibits Significant Metabolism after Oral Dosing in Humans

  2021cited by this paper
• The HECT family of E3 ubiquitin ligases and PTEN.

  2021cited by this paper
• Glucosinolates From Cruciferous Vegetables and Their Potential Role in Chronic Disease: Investigating the Preclinical and Clinical Evidence

  2021cited by this paper
• Peptide Platform as a Powerful Tool in the Fight against COVID-19

  2021cited by this paper
• In silico screening of potent inhibitors against COVID-19 key targets from a library of FDA-approved drugs

  2021cited by this paper
• WWP1 inactivation enhances efficacy of PI3K inhibitors while suppressing their toxicities in breast cancer models.

  2021cited by this paper
• Advances In Drug Therapy For Systemic Lupus Erythematosus.

  2020cited by this paper
• Genetics and Genomics of Breast Cancer: update and translational perspectives.

  2020cited by this paper
• A pneumonia outbreak associated with a new coronavirus of probable bat origin

  2020cited by this paper
• Coronavirus infections and immune responses

  2020cited by this paper
• 3,3’-Diindolylmethane and its derivatives: nature-inspired strategies tackling drug resistant tumors by regulation of signal transduction, transcription factors and microRNAs

  2020cited by this paper
• Cruciferous vegetables: rationale for exploring potential salutary effects of sulforaphane-rich foods in patients with chronic kidney disease.

  2020cited by this paper
• Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

  2020cited by this paper
• Mechanisms Underlying Biological Effects of Cruciferous Glucosinolate-Derived Isothiocyanates/Indoles: A Focus on Metabolic Syndrome

  2020cited by this paper
• Repurposing Drugs for the Management of Patients with Confirmed Coronavirus Disease 2019 (COVID-19).

  2020cited by this paper
• Molecular Targets, Anti-cancer Properties and Potency of Synthetic Indole-3-carbinol Derivatives.

  2019influential reference
• The neuroprotective action of 3,3′-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy that depends on HDAC and AhR/CYP1A1 but not ERα/CYP19A1 signaling

  2019cited by this paper
• Regulatory T-cell levels in systemic lupus erythematosus patients: a meta-analysis

  2019influential reference
• Inhibition of Tumor Growth by Dietary Indole-3-Carbinol in a Prostate Cancer Xenograft Model May Be Associated with Disrupted Gut Microbial Interactions

  2019cited by this paper
• 3,3′-Diindolylmethane Inhibits TNF-α- and TGF-β-Induced Epithelial–Mesenchymal Transition in Breast Cancer Cells

  2019cited by this paper
• Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway

  2019influential reference
• Immunoregulatory effects of indole-3-carbinol on monocyte-derived macrophages in systemic lupus erythematosus: A crucial role for aryl hydrocarbon receptor

  2018cited by this paper
• Comparison of dienogest effects upon 3,3'-diindolylmethane supplementation in models of endometriosis and clinical cases.

  2018cited by this paper
• Indole-3-carbinol: a plant hormone combatting cancer

  2018cited by this paper
• Cruciferous Vegetables and Risk of Cancers of the Gastrointestinal Tract.

  2018cited by this paper
• Indole-3-carbinol is a potent inhibitor of ischemia-reperfusion-induced inflammation.

  2017cited by this paper
• Efficient Synthesis and Biological Activity of Novel Indole Derivatives as VEGFR-2 Tyrosine Kinase Inhibitors

  2017cited by this paper
• Short Chain Fatty Acids Enhance Aryl Hydrocarbon (Ah) Responsiveness in Mouse Colonocytes and Caco-2 Human Colon Cancer Cells

  2017cited by this paper
• Amelioration of Clostridium difficile Infection in Mice by Dietary Supplementation With Indole-3-carbinol

  2017influential reference
• Indole‐3‐carbinol (I3C) analogues are potent small molecule inhibitors of NEDD4‐1 ubiquitin ligase activity that disrupt proliferation of human melanoma cells

  2017influential reference
• A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen

  2017cited by this paper
• Facile Installation of 2-Reverse Prenyl Functionality into Indoles by a Tandem N-Alkylation-Aza-Cope Rearrangement Reaction and Its Application in Synthesis.

  2016cited by this paper
• Facile Installation of 2‐Reverse Prenyl Functionality into Indoles by a Tandem N‐Alkylation—Aza‐Cope Rearrangement Reaction and Its Application in Synthesis.

  2016cited by this paper
• Friedel—Crafts Hydroxyalkylation of Indoles Mediated by Trimethylsilyl Trifluoromethanesulfonate.

  2016cited by this paper
• Anti-androgenic activity of absorption-enhanced 3, 3'-diindolylmethane in prostatectomy patients.

  2016cited by this paper
• Intestinal inflammation and the diet: Is food friend or foe?

  2016cited by this paper
• Indole-3-Carbinol (I3C) and its Major Derivatives: Their Pharmacokinetics and Important Roles in Hepatic Protection.

  2016cited by this paper
• Suppression of Lipid Accumulation by Indole-3-Carbinol Is Associated with Increased Expression of the Aryl Hydrocarbon Receptor and CYP1B1 Proteins in Adipocytes and with Decreased Adipocyte-Stimulated Endothelial Tube Formation

  2016cited by this paper
• Chemopreventive properties of 3,3'-diindolylmethane in breast cancer: evidence from experimental and human studies.

  2016cited by this paper
• Research on cruciferous vegetables, indole-3-carbinol, and cancer prevention: A tribute to Lee W. Wattenberg.

  2016cited by this paper
• First results of the double-blind randomized placebo-controlled multicenter clinical trial of DIM-based therapy designed as personalized approach to reverse prostatic intraepithelial neoplasia (PIN)

  2016cited by this paper
• Inhibition of Testosterone Aromatization by the Indole-3-carbinol Derivative CTet in CYP19A1-overexpressing MCF-7 Breast Cancer Cells.

  2015cited by this paper
• Friedel-Crafts Hydroxyalkylation of Indoles Mediated by Trimethylsilyl Trifluoromethanesulfonate.

  2015cited by this paper
• Classic myrosinase-dependent degradation of indole glucosinolate attenuates fumonisin B1-induced programmed cell death in Arabidopsis.

  2015cited by this paper
• Double-blind randomized placebo-controlled multicenter clinical trial (phase IIa) on diindolylmethane’s efficacy and safety in the treatment of CIN: implications for cervical cancer prevention

  2015cited by this paper
• Role of BioResponse 3,3′-Diindolylmethane in the Treatment of Human Prostate Cancer: Clinical Experience

  2015cited by this paper
• Novel approach to bis(indolyl)methanes: de novo synthesis of 1-hydroxyiminomethyl derivatives with anti-cancer properties.

  2015cited by this paper
• Anticancer efficacy of unique pyridine-based tetraindoles.

  2015influential reference
• Food, immunity, and the microbiome.

  2015cited by this paper
• The Antiproliferative Response of Indole-3-Carbinol in Human Melanoma Cells Is Triggered by an Interaction with NEDD4-1 and Disruption of Wild-Type PTEN Degradation

  2014cited by this paper
• Synthesis and biological evaluation of 2,3'-diindolylmethanes as agonists of aryl hydrocarbon receptor.

  2014cited by this paper
• Attenuation of Carcinogenesis and the Mechanism Underlying by the Influence of Indole-3-carbinol and Its Metabolite 3,3′-Diindolylmethane: A Therapeutic Marvel

  2014cited by this paper
• Effects of Sulforaphane and 3 , 3 9-Diindolylmethane on Genome-Wide Promoter Methylation in Normal Prostate Epithelial Cells and Prostate Cancer Cells

  2014cited by this paper
• Essential role of the cancer stem/progenitor cell marker nucleostemin for indole-3-carbinol anti-proliferative responsiveness in human breast cancer cells

  2014cited by this paper
• Brønsted Acid Catalyzed Bisindolization of α-Amido Acetals: Synthesis and Anticancer Activity of Bis(indolyl)ethanamino Derivatives

  2014cited by this paper
• Attenuation of hyperglycemia-mediated oxidative stress by indole-3-carbinol and its metabolite 3, 3′- diindolylmethane in C57BL/6J mice

  2014cited by this paper
• Indole-3-carbinol induces cMYC and IAP-family downmodulation and promotes apoptosis of Epstein-Barr virus (EBV)-positive but not of EBV-negative Burkitt's lymphoma cell lines.

  2014cited by this paper
• Preclinical antitumor activity of the diindolylmethane formulation in xenograft mouse model of prostate cancer.

  2014cited by this paper
• A new approach for the synthesis of bisindoles through AgOTf as catalyst

  2014cited by this paper
• Phytochemicals from Cruciferous Vegetables, Epigenetics, and Prostate Cancer Prevention

  2013cited by this paper
• Antioxidant Function of Isoflavone and 3,3′-Diindolylmethane: Are They Important for Cancer Prevention and Therapy?

  2013cited by this paper
• OSU-A9, an indole-3-carbinol derivative, induces cytotoxicity in acute myeloid leukemia through reactive oxygen species-mediated apoptosis.

  2013cited by this paper
• Antitumoral activity of indole-3-carbinol cyclic tri- and tetrameric derivatives mixture in human breast cancer cells: in vitro and in vivo studies.

  2013influential reference
• Biomedical Importance of Indoles

  2013cited by this paper
• Micelle promoted multicomponent synthesis of 3-amino alkylated indoles via a Mannich-type reaction in water

  2013influential reference
• Epigenetic Modifications of Nrf2 by 3,3′-diindolylmethane In Vitro in TRAMP C1 Cell Line and In Vivo TRAMP Prostate Tumors

  2013cited by this paper
• The Indole-3-carbinol cyclic tetrameric derivative CTet synergizes with cisplatin and doxorubicin in triple-negative breast cancer cell lines.

  2013cited by this paper
• Mechanistic Studies for Synthesis of Bis(indolyl)methanes: Pd-Catalyzed C–H Activation of Indole–Carboxylic Acids with Benzyl Alcohols in Water

  2013cited by this paper
• The Role of Estrogen Receptor β in Transplacental Cancer Prevention by Indole-3-Carbinol

  2013cited by this paper
• The epigenome as a potential mediator of cancer and disease prevention in prenatal development.

  2013cited by this paper
• DIM (3,3′-diindolylmethane) confers protection against ionizing radiation by a unique mechanism

  2013cited by this paper
• 3,3′-Diindolylmethane Induces G1 Arrest and Apoptosis in Human Acute T-Cell Lymphoblastic Leukemia Cells

  2012cited by this paper
• Novel targets for detection of cancer and their modulation by chemopreventive natural compounds.

  2012cited by this paper
• 3,3′Diindolylmethane Suppresses Vascular Smooth Muscle Cell Phenotypic Modulation and Inhibits Neointima Formation after Carotid Injury

  2012cited by this paper
• Loss of Let-7 Up-Regulates EZH2 in Prostate Cancer Consistent with the Acquisition of Cancer Stem Cell Signatures That Are Attenuated by BR-DIM

  2012cited by this paper
• Induction of Endoplasmic Reticulum Stress Response by the Indole-3-Carbinol Cyclic Tetrameric Derivative CTet in Human Breast Cancer Cell Lines

  2012cited by this paper
• 3,3'-Diindolylmethane, but not indole-3-carbinol, inhibits histone deacetylase activity in prostate cancer cells.

  2012cited by this paper

• Advances in the Understanding of Akt Signaling in Cancers and the Potential of Inhibiting Akt-Driven Tumors Using Small Molecule Inhibitors: An Overview.

  2026cites this paper
• Respiratory syncytial virus downregulates the airway aryl hydrocarbon receptor pathway: implication for the development of a novel therapeutic target.

  2025cites this paper
• 3,3′-Diindolylmethane (DIM): A Molecular Scaffold for Inhibition of WWP1 and WWP2, Members of the NEDD4 Family HECT E3 Ligases

  2025cites this paper
• Feature Reviews in Medicinal Chemistry

  2025cites this paper
• Copper-catalyzed chemoselective C-H functionalization/dearomatization sequence: direct access to indole-based spirocyclic scaffolds.

  2025cites this paper
• Unveiling the Multifaceted Pharmacological Actions of Indole-3-Carbinol and Diindolylmethane: A Comprehensive Review

  2025cites this paper
• Indole‐3‐Carbinol Mechanisms Combating Chemicals and Drug Toxicities

  2025cites this paper
• Brassicaceae microgreens: Pioneering sustainable solutions for functional benefits in modern diets and food security

  2025cites this paper
• Exploring the structural and electronic properties of boron nitride nanotube (BNNT) as nanocarrier for drug delivery applications: DFT approach

  2025cites this paper
• Chemistry, Applications, and Synthesis Methods of Indole Derivatives: A Comprehensive Review

  2025cites this paper
• HOXA10 and HOXA11 Methylation: Epigenetic Barriers to Endometrial Receptivity in ART

  2025cites this paper
• The Senolytic Effect of Indole-3-Carbinol (I3C) on Mouse Embryonic (MEF) and Human Fibroblast Cell Lines

  2024cites this paper
• Role of Phytochemicals in Cardiovascular Disease Management: Insights into Mechanisms, Efficacy, and Clinical Application

  2024cites this paper
• Effect of Indirubin, Indole-3-carbinol and β-Naphthoflavone on the Aryl Hydrocarbon Receptor/Cytochrome 450 Signaling Pathway in Various Human Cell Lines

  2024cites this paper
• Molecular mechanisms of action of DIM and its clinical application

  2024cites this paper
• Solvent effects on the structural, spectroscopic, electronic properties, NCI-RDG analysis molecular docking and molecular dynamics studies of 1-benzyl-indole-3-carbinol

  2024cites this paper
• Overexpression of S30 Ribosomal Protein Leads to Transcriptional and Metabolic Changes That Affect Plant Development and Responses to Stress

  2024cites this paper
• Uremic toxins mediate kidney diseases: the role of aryl hydrocarbon receptor

  2024cites this paper
• Development and Application of a Selective Analytical Method for Indole Metabolites in Urine: Dietary Exposure Biomarkers for Broccoli Consumption.

  2024cites this paper
• Design, synthesis, and anti-inflammatory activity of indole-2-formamide benzimidazole[2,1-b]thiazole derivatives

  2024cites this paper
• Indole-3-Carbinol and Its Derivatives as Neuroprotective Modulators

  2024cites this paper
• Indole-3-carbinol alleviates allergic skin inflammation via periostin/thymic stromal lymphopoietin suppression in atopic dermatitis

  2024cites this paper
• Molecular structure, spectroscopic (FT-IR, NMR and UV-Vis), electronic properties, molecular docking, and molecular dynamics studies on novel thiazolidinone derivative: A potent breast cancer drug

  2024cites this paper
• Palladium-Catalyzed Tsuji–Trost-Type Reaction of 3-Indolylmethylacetates with O, and S Soft Nucleophiles

  2024cites this paper
• Protective Effect of Indole-3-Aldehyde in Murine COVID-19-Associated Pulmonary Aspergillosis

  2024cites this paper
• Evaluation of the anti-inflammatory, analgesic, anti-pyretic and anti-ulcerogenic potentials of synthetic indole derivatives

  2023cites this paper
• Locust bean gum hydrogel containing Indole-3-carbinol nanocapsules has prolonged cutaneous anti-inflammatory action

  2023cites this paper