Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
January-2024 Volume 27 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January-2024 Volume 27 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

Evaluation of dapsone and its synthetic derivative DDS‑13 in cancer in vitro

  • Authors:
    • Griselda A. Cabral‑Pacheco
    • Virginia Flores‑Morales
    • Idalia Garza‑Veloz
    • Miriam Damián‑Sandoval
    • Rosa B. Martínez‑Flores
    • María C. Martínez‑Vázquez
    • Iván Delgado‑Enciso
    • Iram P. Rodriguez‑Sanchez
    • Margarita L. Martinez‑Fierro
  • View Affiliations / Copyright

    Affiliations: Molecular Medicine Laboratory, Academic Unit of Human Medicine and Health Sciences, Autonomous University of Zacatecas, Zacatecas 98160, Mexico, Laboratory of Asymmetric Synthesis and Bio‑Chemoinformatics, Chemical Engineering, Autonomous University of Zacatecas, Zacatecas 98160, Mexico, School of Medicine, University of Colima, Colima 28040, Mexico, Molecular and Structural Physiology Laboratory, School of Biological Sciences, Autonomous University of Nuevo Leon, Nuevo León 66455, Mexico
    Copyright: © Cabral‑Pacheco et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 47
    |
    Published online on: December 4, 2023
       https://doi.org/10.3892/etm.2023.12335
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The present study highlighted the repositioning of the drug dapsone (DDS) for cancer therapy. Due to its mechanism of action, DDS has a dual effect as an antibiotic and as an anti‑inflammatory/immunomodulator; however, at high doses, it has important adverse effects. The derivative DDS‑13 [N,N'‑(sulfonyl bis (4,1‑phenylene)) dioctanamide] was synthesized through an N‑acylation reaction to compare it with DDS. Its cytotoxic effects in cancer cells (DU145 and HeLa) and non‑cancer cells (HDFa) were observed at concentrations ranging 0.01‑100 µM and its physicochemical/pharmacokinetic properties were analyzed using the SwissADME tool. The objectives of the present study were to evaluate the anticancer activity of both DDS and DDS‑13 and to identify the physicochemical and pharmacokinetic properties of DDS‑13. The results showed that DDS‑13 presented a cytotoxic effect in the DU145 cell line (IC50=19.06 µM), while DDS showed a cytotoxic effect on both the DU145 (IC50=11.11 µM) and HeLa (IC50=13.07 µM) cell lines. DDS‑13 appears to be a good cytotoxic candidate for the treatment of prostate cancer, while DDS appears to be a good candidate for both cervical and prostate cancer. Neither candidate showed a cytotoxic effect in non‑cancerous cells. The different pharmacokinetic properties of DDS‑13 make it a new candidate for evaluation in preclinical models for the treatment of cancer.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Catherine Sánchez N: Knowing and understanding the cancer cell: physiopathology of cancer. Rev Méd Clin Las Condes. 24:553–562. 2013.

2 

World Health Organization (WHO): International Agency for Research on Cancer. WHO, Geneva, 2020. https://gco.iarc.fr/today/online-analysis-multi-bars.

3 

Ghose S, Radhakrishnan V and Bhattacharya S: Ethics of cancer care: Beyond biology and medicine. Ecancermedicalscience. 13(911)2019.PubMed/NCBI View Article : Google Scholar

4 

Jarada TN, Rokne JG and Alhajj R: A review of computational drug repositioning: Strategies, approaches, opportunities, challenges, and directions. J Cheminform. 12(46)2020.PubMed/NCBI View Article : Google Scholar

5 

Ross CM: The treatment of acne vulgaris with dapsone. Br J Dermatol. 73:367–370. 1961.PubMed/NCBI View Article : Google Scholar

6 

Reunala T, Hervonen K and Salmi T: Dermatitis herpetiformis: An update on diagnosis and management. Am J Clin Dermatol. 22:329–338. 2021.PubMed/NCBI View Article : Google Scholar

7 

Wozel G and Blasum C: Dapsone in dermatology and beyond. Arch Dermatol Res. 306:103–124. 2014.PubMed/NCBI View Article : Google Scholar

8 

Molinelli E, Paolinelli M, Campanati A, Brisigotti V and Offidani A: Metabolic, pharmacokinetic, and toxicological issues surrounding dapsone. Expert Opin Drug Metab Toxicol. 15:367–379. 2019.PubMed/NCBI View Article : Google Scholar

9 

Boccellino M, Quagliuolo L, Alaia C, Grimaldi A, Addeo R, Nicoletti GF, Kast RE and Caraglia M: The strange connection between epidermal growth factor receptor tyrosine kinase inhibitors and dapsone: From rash mitigation to the increase in anti-tumor activity. Curr Med Res Opin. 32:1839–1848. 2016.PubMed/NCBI View Article : Google Scholar

10 

Kanoh S, Tanabe T and Rubin BK: Dapsone inhibits IL-8 secretion from human bronchial epithelial cells stimulated with lipopolysaccharide and resolves airway inflammation in the ferret. Chest. 140:980–990. 2011.PubMed/NCBI View Article : Google Scholar

11 

Karpel-Massler G, Kast RE, Siegelin MD, Dwucet A, Schneider E, Westhoff MA, Wirtz CR, Chen XY, Halatsch ME and Bolm C: Anti-glioma activity of dapsone and its enhancement by synthetic chemical modification. Neurochemical Res. 42:3382–3389. 2017.PubMed/NCBI View Article : Google Scholar

12 

Lindenberg M, Kopp S and Dressman JB: Classification of orally administered drugs on the World Health Organization model list of essential medicines according to the biopharmaceutics classification system. Eur J Pharm Biopharm. 58:265–278. 2004.PubMed/NCBI View Article : Google Scholar

13 

Gallardo CA, Fan BE, Lim KGE and Kuperan P: Chronic dapsone use causing methemoglobinemia with oxidative hemolysis and dyserythropoiesis. Am J Hematol. 96:1715–1716. 2021.PubMed/NCBI View Article : Google Scholar

14 

Vogel AI, Furniss BS, Hannaford AJ, Smith PW and Tatchell AR: Vogel's textbook of practical organic chemistry. 5th edition. John Wiley & Sons, New York, NY, pp395-469, 1989.

15 

Lidstrom P, Tierney J, Wathey B and Westman J: Microwave assisted organic synthesis-a review. Tetrahedron. 57:9225–9283. 2001.

16 

Lipinski CA, Lombardo F, Dominy BW and Feeney PJ: Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 46:3–26. 2001.PubMed/NCBI View Article : Google Scholar

17 

Ghose AK, Viswanadhan VN and Wendoloski JJ: A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J Comb Chem. 1:55–68. 1999.PubMed/NCBI View Article : Google Scholar

18 

Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW and Kopple KD: Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 45:2615–2623. 2002.PubMed/NCBI View Article : Google Scholar

19 

Egan WJ, Merz KM Jr and Baldwin JJ: Prediction of drug absorption using multivariate statistics. J Med Chem. 43:3867–3877. 2000.PubMed/NCBI View Article : Google Scholar

20 

Muegge I, Heald SL and Brittelli D: Simple selection criteria for drug-like chemical matter. J Med Chem. 44:1841–1846. 2001.PubMed/NCBI View Article : Google Scholar

21 

Sathawane P, Kamal MM, Deotale PR and Mankar H: Nuances of the Papanicolaou stain. Cytojournal. 19(43)2022.PubMed/NCBI View Article : Google Scholar

22 

Swiss Institute of Bioinformatics (SIB): SwissADME. http://www.swissadme.ch/index.php#.

23 

March-Vila E, Pinzi L, Sturm N, Tinivella A, Engkvist O, Chen H and Rastelli G: On the integration of in silico drug design methods for drug repurposing. Front Pharmacol. 8(298)2017.PubMed/NCBI View Article : Google Scholar

24 

do Amaral LH, do Carmo FA, Amaro MI, de Sousa VP, da Silva L, de Almeida GS, Rodrigues CR, Healy AM and Cabral LM: Development and characterization of dapsone cocrystal prepared by scalable production methods. AAPS PharmSciTech. 19:2687–2699. 2018.PubMed/NCBI View Article : Google Scholar

25 

Jornada DH, dos Santos Fernandes GF, Chiba DE, de Melo TR, dos Santos JL and Chung MC: The prodrug approach: A successful tool for improving drug solubility. Molecules. 21(42)2015.PubMed/NCBI View Article : Google Scholar

26 

Day TP, Sil D, Shukla NM, Anbanandam A, Day VW and David SA: Imbuing aqueous solubility to amphotericin B and nystatin with a vitamin. Mol Pharm. 8:297–301. 2011.PubMed/NCBI View Article : Google Scholar

27 

Schilder RJ, Sill MW, Lee YC and Mannel R: A phase II trial of erlotinib in recurrent squamous cell carcinoma of the cervix: A gynecologic oncology group study. Int J Gynecol Cancer. 19:929–933. 2009.PubMed/NCBI View Article : Google Scholar

28 

Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, Coskinas X, Frydenberg M, Hague WE, Horvath LG, et al: Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 381:121–131. 2019.PubMed/NCBI View Article : Google Scholar

29 

Daina A and Zoete V: A BOILED-Egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem. 11:1117–1121. 2016.PubMed/NCBI View Article : Google Scholar

30 

Pillai V, Kadu R, Buch L and Singh VK: Derivatives of dapsone (dap): Synthesis and study on in vitro anticancer activity and DNA laddering against Hep G2 and C6 human cancer cell lines. ChemistrySelect. 2:4382–4391. 2017.

31 

Huang SM, Strong JM, Zhang L, Reynolds KS, Nallani S, Temple R, Abraham S, Habet SA, Baweja RK, Burckart GJ, et al: New era in drug interaction evaluation: US food and drug administration update on CYP enzymes, transporters, and the guidance process. J Clin Pharmacol. 48:662–670. 2008.PubMed/NCBI View Article : Google Scholar

32 

Uetrecht J, Zahid N, Shear NH and Biggar WD: Metabolism of dapsone to a hydroxylamine by human neutrophils and mononuclear cells. J Pharmacol Exp Ther. 245:274–279. 1988.PubMed/NCBI

33 

Tian D and Hu Z: CYP3A4-mediated pharmacokinetic interactions in cancer therapy. Curr Drug Metab. 15:808–817. 2014.PubMed/NCBI View Article : Google Scholar

34 

Guzmán-Ávila R, Avelar M, Márquez EA, Rivera-Leyva JC, Mora JR, Flores-Morales V and Rivera-Islas J: Synthesis, in vitro, and in silico analysis of the antioxidative activity of dapsone imine derivatives. Molecules. 26(5747)2021.PubMed/NCBI View Article : Google Scholar

35 

Zasosov VA: Diacyl derivatives of bis (4-aminophenyl) sulfone. Zhurnal Obshchei Khimii. 17:471–476. 1947.

36 

Hensel; Walter; Buechner O, inventor Polyolefin molding compositions containing diamides, 1967.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Cabral‑Pacheco GA, Flores‑Morales V, Garza‑Veloz I, Damián‑Sandoval M, Martínez‑Flores RB, Martínez‑Vázquez MC, Delgado‑Enciso I, Rodriguez‑Sanchez IP and Martinez‑Fierro ML: Evaluation of dapsone and its synthetic derivative DDS‑13 in cancer <em>in vitro</em>. Exp Ther Med 27: 47, 2024.
APA
Cabral‑Pacheco, G.A., Flores‑Morales, V., Garza‑Veloz, I., Damián‑Sandoval, M., Martínez‑Flores, R.B., Martínez‑Vázquez, M.C. ... Martinez‑Fierro, M.L. (2024). Evaluation of dapsone and its synthetic derivative DDS‑13 in cancer <em>in vitro</em>. Experimental and Therapeutic Medicine, 27, 47. https://doi.org/10.3892/etm.2023.12335
MLA
Cabral‑Pacheco, G. A., Flores‑Morales, V., Garza‑Veloz, I., Damián‑Sandoval, M., Martínez‑Flores, R. B., Martínez‑Vázquez, M. C., Delgado‑Enciso, I., Rodriguez‑Sanchez, I. P., Martinez‑Fierro, M. L."Evaluation of dapsone and its synthetic derivative DDS‑13 in cancer <em>in vitro</em>". Experimental and Therapeutic Medicine 27.1 (2024): 47.
Chicago
Cabral‑Pacheco, G. A., Flores‑Morales, V., Garza‑Veloz, I., Damián‑Sandoval, M., Martínez‑Flores, R. B., Martínez‑Vázquez, M. C., Delgado‑Enciso, I., Rodriguez‑Sanchez, I. P., Martinez‑Fierro, M. L."Evaluation of dapsone and its synthetic derivative DDS‑13 in cancer <em>in vitro</em>". Experimental and Therapeutic Medicine 27, no. 1 (2024): 47. https://doi.org/10.3892/etm.2023.12335
Copy and paste a formatted citation
x
Spandidos Publications style
Cabral‑Pacheco GA, Flores‑Morales V, Garza‑Veloz I, Damián‑Sandoval M, Martínez‑Flores RB, Martínez‑Vázquez MC, Delgado‑Enciso I, Rodriguez‑Sanchez IP and Martinez‑Fierro ML: Evaluation of dapsone and its synthetic derivative DDS‑13 in cancer <em>in vitro</em>. Exp Ther Med 27: 47, 2024.
APA
Cabral‑Pacheco, G.A., Flores‑Morales, V., Garza‑Veloz, I., Damián‑Sandoval, M., Martínez‑Flores, R.B., Martínez‑Vázquez, M.C. ... Martinez‑Fierro, M.L. (2024). Evaluation of dapsone and its synthetic derivative DDS‑13 in cancer <em>in vitro</em>. Experimental and Therapeutic Medicine, 27, 47. https://doi.org/10.3892/etm.2023.12335
MLA
Cabral‑Pacheco, G. A., Flores‑Morales, V., Garza‑Veloz, I., Damián‑Sandoval, M., Martínez‑Flores, R. B., Martínez‑Vázquez, M. C., Delgado‑Enciso, I., Rodriguez‑Sanchez, I. P., Martinez‑Fierro, M. L."Evaluation of dapsone and its synthetic derivative DDS‑13 in cancer <em>in vitro</em>". Experimental and Therapeutic Medicine 27.1 (2024): 47.
Chicago
Cabral‑Pacheco, G. A., Flores‑Morales, V., Garza‑Veloz, I., Damián‑Sandoval, M., Martínez‑Flores, R. B., Martínez‑Vázquez, M. C., Delgado‑Enciso, I., Rodriguez‑Sanchez, I. P., Martinez‑Fierro, M. L."Evaluation of dapsone and its synthetic derivative DDS‑13 in cancer <em>in vitro</em>". Experimental and Therapeutic Medicine 27, no. 1 (2024): 47. https://doi.org/10.3892/etm.2023.12335
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team