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Eur J Pharmacol 2021 May 8;904:174143. Epub 2021 May 8.

Military Institute of Hygiene and Epidemiology, 01-163, Warsaw, Poland; Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research (CBP), Medical University of Warsaw, 02-097, Warsaw, Poland.

Disulfiram (DSF) is a well-known anti-alcohol agent that inhibits aldehyde dehydrogenase and results in extreme 'hangover' symptoms when consumed with alcohol This drug, however, has been suggested as useful in other forms of drug addiction due to its beneficial potential in both drug abuse reduction and withdrawal However, among other drugs used in alcohol dependence, it carries the greatest risk of pharmacological interactions Concomitant use of DSF and central nervous system stimulants usually leads to harmful, undesirable effects To date, there is still limited data regarding the detailed safety profile of DSF as a concomitant drug In this review article, we outline the current state of knowledge about DSF, its broad pharmacological action, as well as therapeutic effects, with a particular emphasis on the molecular understanding of its potential pharmacodynamic interactions with common addictive substances (eg, alcohol, cocaine, cannabinoids, opioids) supported by relevant examples. Read More

Life (Basel) 2021 Apr 26;11(5). Epub 2021 Apr 26.

Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China.

Disulfiram (DSF) is an important drug for the treatment and management of alcohol dependency. This drug has been approved by US-FDA, and its activity against the tumor is dependent on copper ion (Cu). However, the copper toxicity (caused via external copper) and its intrinsic anfractuous distribution in the human body have adversely suppressed the mechanism of DSF in in vivo. Read More

J Biochem 2021 Apr 1. Epub 2021 Apr 1.

Department of Orthopaedics, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China.

Given the huge cost, long research and development (R&D) time and uncertain side effects of discovering new drugs, drug repositioning of those approved to treat diseases clinically as new drugs for other pathological conditions, especially cancers, is a potential alternative strategy. Disulfiram (DSF), an old drug used to treat alcoholism, has been found to exhibit anticancer activity and improve chemotherapeutic efficacy in cancers by an increasing number of studies. In addition, the combination of DSF and copper may be a more effective therapeutic strategy. Read More

Front Cell Infect Microbiol 2021 11;11:633194. Epub 2021 Mar 11.

Division of Infectious Diseases & International Health, Department of Medicine, University of Virginia, Charlottesville, VA, United States.

Parasitic infections contribute significantly to worldwide morbidity and mortality. Antibiotic treatment is essential for managing patients infected with these parasites since control is otherwise challenging and there are no vaccines available for prevention. However, new antimicrobial therapies are urgently needed as significant problems exist with current treatments such as drug resistance, limited options, poor efficacy, as well as toxicity. Read More

Carbohydr Polym 2021 Jun 23;261:117846. Epub 2021 Feb 23.

School of Life Science, Zhengzhou University, 100 Science Road, Zhengzhou, 450001, PR China. Electronic address:

In the clinical treatment of cancer, improving the effectiveness and targeting of drugs has always been a bottleneck problem that needs to be solved. In this contribution, inspired by the targeted inhibition on cancer from combination application of disulfiram and divalent copper ion (Cu), we optimized the concentration of disulfiram and Cu ion for inhibiting esophageal cancer cells, and loaded them in hyaluronic acid (HA)/polyethyleneimine (PEI) nanoparticles with specific scales, in order to improve the effectiveness and targeting of drugs. The in vitro cell experiments demonstrated that more drug loaded HA/PEI nanoparticles accumulated to the esophageal squamous cell carcinoma (Eca109) and promoted higher apoptosis ratio of Eca109. Read More

ACS Nano 2021 04 22;15(4):6457-6470. Epub 2021 Mar 22.

Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai 200444, People's Republic of China.

Disulfiram (DSF), a U.S. Food and Drug Administration (FDA)-approved drug for the treatment of chronic alcoholism, is also used as an antitumor drug in combination with Cu ions. Read More

Int J Pharm 2021 Mar 22;597:120250. Epub 2021 Jan 22.

Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China. Electronic address:

Glioblastoma (GBM) is a difficult-to-treat cancer, likely attributed to the blood brain barrier and drug resistance. Nose-to-brain drug delivery is a direct and non-invasive pathway for brain targeting with low systemic toxicity. Disulfiram (DSF) has shown its effectiveness against GBM, especially with copper ion (Cu). Read More

Mater Sci Eng C Mater Biol Appl 2021 Feb 27;119:111452. Epub 2020 Aug 27.

Department of Analytical Chemistry, Faculty of Pharmacy, Atatürk University, 25240 Erzurum, Turkey.

Disulfiram (DSF), one of the members of the dithiocarbamate family, is a reactive species (RS) generator and is capable of inducing cancer cell death in breast cancer. However, it is hydrophobic and highly degradable in blood. Therefore, drug delivery systems would be of great benefit in supporting the selective accumulation of DSF in tumor cells. Read More

Front Cell Dev Biol 2020 5;8:590540. Epub 2020 Nov 5.

Max Delbrück Center for Molecular Medicine, Berlin, Germany.

Excessive ethanol exposure can cause mitochondrial and cellular toxicity. In order to discover potential counteracting interventions, it is essential to develop assays capable of capturing the consequences of ethanol exposure in human neurons, and particularly dopaminergic neurons that are crucial for the development of alcohol use disorders (AUD). Here, we developed a novel high-throughput (HT) assay to quantify mitochondrial and neuronal toxicity in human dopaminergic neuron-containing cultures (DNs) from induced pluripotent stem cells (iPSCs). Read More

Alcohol Alcohol 2021 Jan;56(1):42-46

Drug De-Addiction and Treatment CentreDepartment of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Aims: We conducted a cross-sectional survey to estimate the prevalence and clinical manifestation of disulfiram ethanol reaction (DER) and isopropanol toxicity (IT) in patients with alcohol use disorders, on disulfiram. Alcohol-based hand rub contains either ethanol or isopropanol or both. COVID-19 pandemic has led to wide scale usage of sanitizers. Read More

Biochem Pharmacol 2020 12 23;182:114231. Epub 2020 Sep 23.

Servicio de Enfermedades Infecciosas, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) and Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain; Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá de Henares, 28871 Alcalá de Henares, Spain.

Human immunodeficiency virus (HIV) remains incurable due to latent reservoirs established in non-activated CD4 T cells. Current efforts to achieve a functional cure rely on immunomodulatory strategies focused on enhancing the functions of cytotoxic cells. Implementation of these actions requires a coordinated activation of the viral transcription in latently infected cells so that the reservoir became visible and accessible to cytotoxic cells. Read More

ACS Appl Mater Interfaces 2020 Oct 7;12(42):47289-47298. Epub 2020 Oct 7.

Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350108, P. R. China.

In recent times, the combination therapy has garnered enormous interest owing to its great potential in clinical research. It has been reported that disulfiram, a clinical antialcoholism drug, could be degraded to diethyldithiocarbamate (DDTC) and subsequently result in the copper-DDTC complex (Cu(DDTC)) toward ablating cancer cells. In addition, the ultrasmall copper sulfide nanodots (CuS NDs) have shown great potential in cancer treatment because of their excellent photothermal and photodynamic therapeutic efficiencies. Read More

Curr Med Chem 2020 ;27(42):7222-7233

Department of Life Sciences, University of Trieste, Via Giorgeri 1, 34127 Trieste, Italy

Background: Ovary Carcinoma (OC) is the most lethal gynecological neoplasm due to the late diagnoses and to the common development of resistance to platinum-based chemotherapy. Thus, novel therapeutic approaches are urgently required. In this regard, the strategy of drug repurposing is becoming attractive. Read More

Cell Commun Signal 2020 07 11;18(1):111. Epub 2020 Jul 11.

Queens College and Graduate Center, City University of New York, 65-30 Kissena Blvd, NSB E143, Flushing, NY, 11367, USA.

Background: Cells taken from mouse embryos before sex differentiation respond to insults according to their chromosomal sex, a difference traceable to differential methylation. We evaluated the mechanism for this difference in the controlled situation of their response to ethanol.

Methods: We evaluated the expression of mRNA for alcohol dehydrogenase (ADH), aldehyde dehyrogenases (ALDH), and a cytochrome P450 isoenzyme (Cyp2e1) in male and female mice, comparing the expressions to toxicity under several experimental conditions evaluating redox and other states. Read More

Curr Pharm Des 2020 ;26(35):4461-4466

IVIC, Cancer Cell Biology Laboratory, CMBC, Caracas 1020A, Venezuela.

Background: Copper (Cu) is a transition metal active in Fenton redox cycling from reduced Cu+ and H2O2, to oxidized Cu2+ and the hydroxyl radical (·OH) highly reactive oxygen species (ROS). At homeostatic Cu levels, ROS promote cell proliferation, migration, angiogenesis, and wound repair. To limit ROS toxicity, cells use Cu-dependent chaperone proteins, Cu-binding ceruloplasmin, and Cu-modulated enzymes like superoxide dismutases (SOD) like SOD1 and SOD3 to scavenge excess superoxide anions which favour Cu+ reduction, and mitochondrial cytochrome c oxidase, important in aerobic energy production. Read More

Vascul Pharmacol 2020 08 22;131:106762. Epub 2020 Jun 22.

Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, United States of America; Department of Physiology, Wayne State University, Detroit, MI 48202, United States of America. Electronic address:

4-hydroxynonenal (4HNE) is a reactive aldehyde, which is involved in oxidative stress associated pathogenesis. The cellular toxicity of 4HNE is mitigated by aldehyde dehydrogenase (ALDH) 2. Thus, we hypothesize that ALDH2 inhibition exacerbates 4HNE-induced decrease in coronary endothelial cell (EC) migration in vitro. Read More

Indian J Crit Care Med 2020 Mar;24(3):203-205

Department of Pharmacology, Pandit Bhagwat Dayal Sharma Postgraduate Institute of Medical Sciences, Rohtak, Haryana, India.

Aim: To determine the significance of acute disulfiram poisoning in pediatric population.

Background: Disulfiram poisoning in children is uncommon, can occur in children who have ingested large amount of drug because of careless and unsafe storage. Only few cases have been reported in literature. Read More

Angew Chem Int Ed Engl 2020 12 17;59(49):21829-21838. Epub 2020 Sep 17.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China.

The high morbidity and mortality of cancer requires innovative therapeutics. Very recently, several old drugs approved by the U.S. Read More

Bioorg Med Chem Lett 2020 06 28;30(11):127148. Epub 2020 Mar 28.

Department of Chemistry, Duke University, Durham, NC 27708-0354 USA. Electronic address:

Disulfiram in conjunction with copper has been shown to be a potent anticancer agent. However, disulfiram's therapeutic potential in prostate cancer is hindered by off-target effects due to its reactive and nucleophilic thiol-containing component, diethyldithiocarbamate (DTC). To minimize undesirable reactivity, we have strategically blocked the thiol moiety in DTC with a cleavable p-aminobenzyl (pAB) group linked to peptide substrates recognized by prostate specific antigen (PSA). Read More

Nanoscale 2020 Apr 1;12(15):8139-8146. Epub 2020 Apr 1.

School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210089, PR China.

Recent studies have suggested that the anticancer activity of disulfiram (DSF, an FDA-approved alcohol-abuse drug) is Cu-dependent. Low system toxicity and explicit pharmacokinetic characteristics of DSF necessitate safe and effective Cu supplementation in local lesion for further applications. Herein, we presented a new conceptual 'nanosized coordination transport' strategy of Cu(ii) that was realized in porphyrin-based metal-organic frameworks, Sm-TCPP, with strong binding ability to Cu(ii) due to their coordination interactions. Read More

Free Radic Biol Med 2020 04 4;150:1-11. Epub 2020 Feb 4.

Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA. Electronic address:

Therapies for lung cancer patients initially elicit desirable responses, but the presence of hypoxia and drug resistant cells within tumors ultimately lead to treatment failure. Disulfiram (DSF) is an FDA approved, copper chelating agent that can target oxidative metabolic frailties in cancer vs. normal cells and be repurposed as an adjuvant to cancer therapy. Read More

Cell Biochem Funct 2020 Apr 13;38(3):290-299. Epub 2020 Jan 13.

Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan.

Coronary endothelial cell (EC) dysfunction including defective angiogenesis is reported in cardiac diseases. 4-Hydroxynonenal (4HNE) is a lipid peroxidation product, which is increased in cardiac diseases and implicated in cellular toxicity. Aldehyde dehydrogenase (ALDH) 2 is a mitochondrial enzyme that metabolizes 4HNE and reduces 4HNE-mediated cytotoxicity. Read More

Biomolecules 2020 01 1;10(1). Epub 2020 Jan 1.

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow region 142290, Russia.

We have shown that hydroxycobalamin (vitamin В) increases the toxicity of diethyldithiocarbamate (DDC) to tumor cells by catalyzing the formation of disulfiram (DSF) oxi-derivatives. The purpose of this study was to elucidate the mechanism of tumor cell death induced by the combination DDC + В. It was found that cell death induced by DDC + B differed from apoptosis, autophagy, and necrosis. Read More

Clin Toxicol (Phila) 2020 09 26;58(9):922-925. Epub 2019 Dec 26.

Department of Medical and Toxicological Critical Care, Federation of Toxicology APHP, Lariboisière Hospital, University of Paris, Paris, France.

Disulfiram-ethanol reaction (DER) due to acetaldehyde accumulation occurs after drinking ethanol during disulfiram therapy. DER may result in life-threatening toxicity requiring urgent critical care. Fomepizole, an alcohol dehydrogenase inhibitor used to treat toxic alcohol poisoning, has been suggested for treating DER by preventing the metabolism of ethanol to acetaldehyde. Read More

Antimicrob Agents Chemother 2020 02 21;64(3). Epub 2020 Feb 21.

Division of Infectious Diseases, Veterans Affairs Western New York Healthcare System, Buffalo, New York, USA.

Many antibiotics carry caution stickers that warn against alcohol consumption. Data regarding concurrent use are sparse. An awareness of data that address this common clinical scenario is important so health care professionals can make informed clinical decisions and address questions in an evidence-based manner. Read More

Environ Toxicol Pharmacol 2020 Feb 16;74:103300. Epub 2019 Nov 16.

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA. Electronic address:

Dithiocarbamates (DTCs) like mancozeb (MZ) and disulfiram (DS) are used throughout agriculture and medicine and have been implicated in neurotoxicity. Little research has been studied on the reported myopathies caused by these compounds. Their pathogenesis and mechanism of muscle toxicity has not been fully studied. Read More

Chem Commun (Camb) 2019 Nov;55(92):13896-13899

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.

Here, we report the rational design of a H2O2-responsive diethyldithiocarbamate (DTC)-based prodrug, which chelated Cu(ii) to form Cu(DTC)2 with a high anticancer activity in a tumor-microenvironment and induced oxidative stress amplification, showing superior antitumor toxicity to disulfiram. Read More

Int J Mol Sci 2019 Oct 22;20(20). Epub 2019 Oct 22.

Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan.

Copper is an essential trace element within cells, but it also exerts cytotoxic effects through induction of reactive oxygen species (ROS) production. To determine the mechanisms underlying copper-induced ROS production, we examined the effects of copper sulfate in HeLa cells. Exposure to copper sulfate led to dose-dependent decreases in HeLa cell viability, along with increases in the subG1 and G2/M populations and corresponding decreases in the G1 population. Read More

Med Hypotheses 2019 Oct 26;131:109289. Epub 2019 Jun 26.

Biochemistry and Molecular Biology, Paris-Descartes University, 26 rue de Chartres, 92200 Neuilly, France. Electronic address:

Mental retardation is a progressive condition in Down syndrome: intelligence starts to decline linearly within the first year. This phenomenon could be related to the overproduction of a toxic compound, hydrogen sulfide. Indeed, a gene located on chromosome 21 controls the production of cystathionine-β-synthase, an enzyme involved in hydrogen sulfide production in the central nervous system. Read More

Front Microbiol 2019 30;10:1720. Epub 2019 Jul 30.

Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL, United States.

Rationale: Mycoplasmas represent important etiologic agents of many human diseases. Due to increasing antimicrobial resistance and slow rate of novel discovery, unconventional methods of drug discovery are necessary. Copper ions are utilized in host microbial killing, and bacteria must regulate intracellular Cu concentrations to avoid toxicity. Read More