Promin

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Promin
Promin Molecular Structure Skeletal.svg
Promin Molecular Structure Spacefill.png
Clinical data
Other namesSodium glucosulfone, Aceprosol, Promanide, Tasmin, Sulfona P
Identifiers
  • 2,3,4,5,6-pentahydroxy-1-[4-[4-[(2,3,4,5,6-pentahydroxy-1-sulfohexyl)amino]phenyl]sulfonylanilino]hexane-1-sulfonic acid
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C24H36N2O18S3
Molar mass 736.73 g·mol−1
3D model (JSmol)
  • [Na+].[Na+].[O-]S(=O)(=O)[C@H](Nc1ccc(cc1)S(=O)(=O)c2ccc(N[C@@H](S([O-])(=O)=O)[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO)cc2)[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
  • InChI=1S/C24H36N2O18S3.2Na/c27-9-15(29)17(31)19(33)21(35)23(46(39,40)41)25-11-1-5-13(6-2-11)45(37,38)14-7-3-12(4-8-14)26-24(47(42,43)44)22(36)20(34)18(32)16(30)10-28;;/h1-8,15-36H,9-10H2,(H,39,40,41)(H,42,43,44);;/q;2*+1/p-2/t15-,16-,17-,18-,19+,20+,21-,22-,23+,24+;;/m1../s1 X mark.svgN
  • Key:NLLGJEMIZSAJFN-XRAGNMTMSA-L X mark.svgN
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Promin, or sodium glucosulfone is a sulfone drug that was investigated for the treatment of malaria, [1] tuberculosis [2] and leprosy. [3] [4] It is broken down in the body to dapsone, which is the therapeutic form. [5]

Contents

History

The first synthesis of Promin is sometimes credited to Edward Tillitson and Benjamin F. Tullar of Parke, Davis, & Co. pharmaceuticals in August 1937. [6] [7] However, although Parke-Davis did in fact synthesize the compound, it seems certain that they were not the first; in cooperation with J. Wittmann, Emil Fromm synthesised various sulfone compounds in 1908, including both dapsone and some of its derivatives, such as promin. Fromm and Wittmann however were engaged on chemical rather than medical work, and no-one investigated the medical value of such compounds until some decades afterwards. [7] The medical evaluation of sulfones was inspired by the discovery of the unprecedented value of synthetic compounds such as sulfonamides in treating microbial diseases. Early investigations yielded disappointing results, but subsequently promin and dapsone proved valuable in treating mycobacterial diseases. They were the first treatments to show more than a glimmer of hope of controlling such infections. [8]

Initially, Promin appeared to be safer than dapsone, so it was further investigated at the Mayo Clinic as a treatment for tuberculosis in a guinea pig model. [9] Because it was already known that leprosy and tuberculosis were both caused by mycobacteria ( Mycobacterium leprae and Mycobacterium tuberculosis , respectively), Guy Henry Faget of the National Leprosarium in Carville, Louisiana, requested information about the drug from Parke-Davis. They, in turn, informed him of the work being done on leprosy in rats by Edmund Cowdry at the Washington University School of Medicine. His successful results, published in 1941, convinced Faget to begin human studies, both with promin and sulfoxone sodium, a related compound from Abbott Laboratories. The initial trials were on six volunteers, and were then expanded and replicated in different locations. Despite severe side effects that caused the initial tests to be suspended temporarily, the drug was shown to be effective. [9] [10] This breakthrough was reported worldwide, and led to a reduction in the stigma attached to leprosy, and consequent better treatment of patients, at the time still referred to as "inmates", and forbidden from using public transport. [11]

Pharmacology

Promin is heat-stable and water-soluble, and can therefore be heat-sterilized. [12] It can be injected intravenously, [12] and is available in ampules. [13]

Beyond its solubility, however, promin was later found to have no real advantages over the simpler compound dapsone (which is administered in tablet form). Promin and other sulfones can also not be used as substitutes for dapsone when intolerance develops, as this is a general reaction to sulfones, and not specific to dapsone. [14]

Today, the drugs of choice for treating leprosy are dapsone, rifampicin and clofazimine. [15]

Related Research Articles

<span class="mw-page-title-main">Leprosy</span> Chronic infection caused by mycobacteria leprae or lepromatosis

Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria Mycobacterium leprae or Mycobacterium lepromatosis. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve damage may result in a lack of ability to feel pain, which can lead to the loss of parts of a person's extremities from repeated injuries or infection through unnoticed wounds. An infected person may also experience muscle weakness and poor eyesight. Leprosy symptoms may begin within one year, but, for some people, symptoms may take 20 years or more to occur.

<span class="mw-page-title-main">Mycobacterial cervical lymphadenitis</span> Human medical condition

The disease mycobacterial cervical lymphadenitis, also known as scrofula and historically as king's evil, involves a lymphadenitis of the cervical lymph nodes associated with tuberculosis as well as nontuberculous (atypical) mycobacteria.

<i>Mycobacterium tuberculosis</i> Species of pathogenic bacteria that causes tuberculosis

Mycobacterium tuberculosis, also known as Koch's bacillus, is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, M. tuberculosis has an unusual, waxy coating on its cell surface primarily due to the presence of mycolic acid. This coating makes the cells impervious to Gram staining, and as a result, M. tuberculosis can appear weakly Gram-positive. Acid-fast stains such as Ziehl–Neelsen, or fluorescent stains such as auramine are used instead to identify M. tuberculosis with a microscope. The physiology of M. tuberculosis is highly aerobic and requires high levels of oxygen. Primarily a pathogen of the mammalian respiratory system, it infects the lungs. The most frequently used diagnostic methods for tuberculosis are the tuberculin skin test, acid-fast stain, culture, and polymerase chain reaction.

<i>Mycobacterium</i> Genus of bacteria

Mycobacterium is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy in humans. The Greek prefix myco- means 'fungus', alluding to this genus' mold-like colony surfaces. Since this genus has cell walls with a waxy lipid-rich outer layer that contains high concentrations of mycolic acid, acid-fast staining is used to emphasize their resistance to acids, compared to other cell types.

<i>Mycobacterium leprae</i> Bacterium that causes leprosy

Mycobacterium leprae is one of the two species of bacteria that cause Hansen's disease (leprosy), a chronic but curable infectious disease that damages the peripheral nerves and targets the skin, eyes, nose, and muscles.

<span class="mw-page-title-main">Dapsone</span> Antibiotic medication

Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS), is an antibiotic commonly used in combination with rifampicin and clofazimine for the treatment of leprosy. It is a second-line medication for the treatment and prevention of pneumocystis pneumonia and for the prevention of toxoplasmosis in those who have poor immune function. Additionally, it has been used for acne, dermatitis herpetiformis, and various other skin conditions. Dapsone is available both topically and by mouth.

Nontuberculous mycobacteria (NTM), also known as environmental mycobacteria, atypical mycobacteria and mycobacteria other than tuberculosis (MOTT), are mycobacteria which do not cause tuberculosis or leprosy/Hansen's disease. NTM are able to cause pulmonary diseases that resemble tuberculosis. Mycobacteriosis is any of these illnesses, usually meant to exclude tuberculosis. They occur in many animals, including humans and are commonly found in soil and water.

<span class="mw-page-title-main">Rifampicin</span> Antibiotic medication

Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), Mycobacterium avium complex, leprosy, and Legionnaires' disease. It is almost always used together with other antibiotics with two notable exceptions: when given as a "preferred treatment that is strongly recommended" for latent TB infection; and when used as post-exposure prophylaxis to prevent Haemophilus influenzae type b and meningococcal disease in people who have been exposed to those bacteria. Before treating a person for a long period of time, measurements of liver enzymes and blood counts are recommended. Rifampicin may be given either by mouth or intravenously.

<span class="mw-page-title-main">Sulfone</span> Organosulfur compound of the form >S(=O)2

In organic chemistry, a sulfone is a organosulfur compound containing a sulfonyl functional group attached to two carbon atoms. The central hexavalent sulfur atom is double-bonded to each of two oxygen atoms and has a single bond to each of two carbon atoms, usually in two separate hydrocarbon substituents.

<span class="mw-page-title-main">Erythema nodosum</span> Medical condition

Erythema nodosum (EN) is an inflammatory condition characterized by inflammation of the fat cells under the skin, resulting in tender red nodules or lumps that are usually seen on both shins. It can be caused by a variety of conditions, and typically resolves spontaneously within 30 days. It is common in young people aged 12–20 years.

<span class="mw-page-title-main">Clofazimine</span> Medication

Clofazimine, sold under the brand name Lamprene, is a medication used together with rifampicin and dapsone to treat leprosy. It is specifically used for multibacillary (MB) leprosy and erythema nodosum leprosum. Evidence is insufficient to support its use in other conditions though a retrospective study found it 95% effective in the treatment of Mycobacterium avium complex (MAC) when administered with a macrolide and ethambutol, as well as the drugs amikacin and clarithromycin. However, in the United States, clofazimine is considered an orphan drug, is unavailable in pharmacies, and its use in the treatment of MAC is overseen by the Food and Drug Administration. It is taken orally.

<i>Mycobacterium avium-intracellulare</i> infection Medical condition

Mycobacterium avium-intracellulare infection (MAI) is an atypical mycobacterial infection, i.e. one with nontuberculous mycobacteria or NTM, caused by Mycobacterium avium complex (MAC), which is made of two Mycobacterium species, M. avium and M. intracellulare. This infection causes respiratory illness in birds, pigs, and humans, especially in immunocompromised people. In the later stages of AIDS, it can be very severe. It usually first presents as a persistent cough. It is typically treated with a series of three antibiotics for a period of at least six months.

<i>Mycobacterium kansasii</i> Species of bacterium

Mycobacterium kansasii is a bacterium in the Mycobacterium genus. It is an environmental bacteria that causes opportunistic infections in humans, and is one of the leading mycobacterial causes of human disease after tuberculosis and leprosy.

<span class="mw-page-title-main">Acedapsone</span> Antimicrobial drug

Acedapsone (INN) is an antimicrobial drug, which also has antimalarial activity.

A leprostatic agent is a drug that interferes with proliferation of the bacterium that causes leprosy.

<span class="mw-page-title-main">Lepromatous leprosy</span> Medical condition

Lepromatous leprosy is a form of leprosy characterized by pale macules in the skin.

Guy Henry Faget (1891–1947) was an American medical doctor who revolutionalized the treatment of leprosy, by demonstrating the efficacy of promin, as described in a paper published in 1943. Promin is a sulfone compound, synthesized by Feldman and his co-workers in 1940, which is a chemotherapeutic agent that was determined to be effective against tuberculosis in experimental animals. He was the grandson of Jean Charles Faget, and father of Maxime Faget.

Hydnocarpus wightianus or chaulmoogra is a tree in the Achariaceae family. Hydnocarpus wightiana seed oil has been widely used in traditional Indian medicine, especially in Ayurveda, and in Chinese traditional medicine for the treatment of leprosy. It entered early Western medicine in the nineteenth century before the era of sulfonamides and other antibiotics for the treatment of several skin diseases and leprosy. The oil was prescribed for leprosy as a mixture suspended in gum or as an emulsion.

<span class="mw-page-title-main">History of leprosy</span>

The history of leprosy was traced to its origins by an international team of 22 geneticists using comparative genomics of the worldwide distribution of Mycobacterium leprae. Monot et al. (2005) determined that leprosy originated in East Africa or the Near East and traveled with humans along their migration routes, including those of trade in goods and slaves. The four strains of M. leprae are based in specific geographic regions where each predominantly occurs:

<span class="mw-page-title-main">Lalita Ramakrishnan</span> Indian-American microbiologist

Lalita Ramakrishnan is an Indian-born American microbiologist who is known for her contributions to the understanding of the biological mechanism of tuberculosis. As of 2019 she serves as a professor of Immunology and Infectious Diseases at the University of Cambridge, where she is also a Wellcome Trust Principal Research Fellow and a practicing physician. Her research is conducted at the MRC Laboratory of Molecular Biology, where she serves as the Head of the Molecular Immunity Unit of the Department of Medicine embedded at the MRC LMB. Working with Stanley Falkow at Stanford, she developed the strategy of using Mycobacterium marinum infection as a model for tuberculosis. Her work has appeared in a number of journals, including Science, Nature, and Cell. In 2018 and 2019 Ramakrishnan coauthored two influential papers in the British Medical Journal (BMJ) arguing that the widely accepted estimates of the prevalence of latent tuberculosis—estimates used as a basis for allocation of research funds—are far too high. She is married to Mark Troll, a physical chemist.

References

  1. ↑ Slater LB (2009). War and disease: biomedical research on malaria in the twentieth century. New Brunswick, N.J: Rutgers University Press. p. 102. ISBN   978-0-8135-4438-0.
  2. ↑ Lilienfeld D, Schneider D (2011). Public Health: The Development of a Discipline. Vol. 2 Twentieth-Century Challenges. New Brunswick, N.J: Rutgers University Press. p. 351. ISBN   978-0-8135-5009-1.
  3. ↑ Faget GH, Pogge RC, Johansen FA, Dinan JF, Prejean BM, Eccles CG (November 1943). "The Promin Treatment of Leprosy". Public Health Reports. 58 (48). Washington, D.C.: 1729–1741. doi:10.2307/4584691. JSTOR   4584691. PMC   2017027 . PMID   19315949.
  4. ↑ Faget GH, Pogge RC, Johansen FA, Dinan JF, Prejean BM, Eccles CG (1966). "Reprint: The promin treatment of leprosy. A progress report". International Journal of Leprosy and Other Mycobacterial Diseases. 34 (3): 298–310. PMID   5950351.
  5. ↑ McDougall AC (June 1979). "Dapsone". Clinical and Experimental Dermatology. 4 (2): 139–42. doi:10.1111/j.1365-2230.1979.tb01608.x. PMID   498567.
  6. ↑ Johansen EA. "Current Data on Promin Therapy; reprinted in The Star October-December 2003" (PDF).
  7. 1 2 Wozel G (1989). "The story of sulfones in tropical medicine and dermatology". International Journal of Dermatology. 28 (1): 17–21. doi:10.1111/j.1365-4362.1989.tb01301.x. PMID   2645226. S2CID   30991934.
  8. ↑ Desikan KV (January 2003). "Multi-drug Regimen in Leprosy and its impact on Prevalence of the Disease". Medical Journal, Armed Forces India. 59 (1): 2–4. doi:10.1016/S0377-1237(03)80092-8. PMC   4925770 . PMID   27407445.
  9. 1 2 Sneader W (2005). Drug discovery: a history. New York: Wiley. ISBN   978-0-471-89979-2.
  10. ↑ Tayman J (2006). The Colony. Simon and Schuster. p. 252. ISBN   0-471-89979-8.
  11. ↑ "Hope for Lepers". Time Magazine. 30 December 1946. Retrieved 22 July 2011.
  12. 1 2 Singh R (2002). Synthetic Drugs. Mittal Publications. p. 291. ISBN   978-81-7099-831-0.
  13. ↑ Clinical Leprosy. Jaypee Brothers Medical Publishers (P) Ltd. 2004. ISBN   978-81-8061-283-1.
  14. ↑ Textbook Of Pharmacology. Elsevier India Pvt. Ltd. 2008. pp. X–87. ISBN   978-81-312-1158-8.
  15. ↑ Ravina E, Kubinyi H (2011). The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs. John Wiley & Sons. p. 80. ISBN   978-3-527-32669-3.
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