Lucanthone

Lucanthone
Clinical data
ATC code
  • none
Identifiers
  • 1-{[2-(diethylamino)ethyl]amino}-4-methyl-9H-thioxanthen-9-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEBI
CompTox Dashboard (EPA)
ECHA InfoCard100.006.849
Chemical and physical data
FormulaC20H24N2OS
Molar mass340.49 g·mol−1
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Lucanthone (Miracil D, Myracyl D) is a drug used to treat parasitic diseases such as schistosomiasis,[1][2][3] which was invented in 1938 by Hans Mauss and colleagues at Bayer AG.[4][5] It is a prodrug and is converted to the active metabolite hycanthone.[6][7] It is no longer commonly used in humans due to hepatotoxicity,[8] especially after the subsequent development of safer drugs with similar efficacy such as praziquantel.

Mechanism of action

Hycanthone binds to acetylcholine receptors in the worm[9] and results in increased sensitivity to stimulation by 5-HT causing increase in motility, paired worms are separated and reproduction is stopped. It causes damage of the integument and vitelline duct.

Research

Lucanthone also shows anti-cancer activity, and while it has never been approved for medical use as a chemotherapy drug due to its toxicity, it has been tested in human clinical trials as an adjuvant therapy to increase the effectiveness of other chemotherapy medications, and continues to be used in cancer research.[10][11][12][13][14][15][16][17][18][19][20]

Synthesis

The original synthesis route by Mauss and colleagues produces a mixture of isomers which then needs to be separated,[21] this was subsequently improved upon in the 1950s.[22]

References

  1. ^ Blair DM (1958). "Lucanthone hydrochloride; a review". Bulletin of the World Health Organization. 18 (5–6): 989–1010. PMC 2537946. PMID 13573122.
  2. ^ Standen O (2013) [1963]. "Chemotherapy of Helminthic Infections". In Schnitzer RJ, Hawking F (eds.). Experimental chemotherapy. Vol. 1. New York, New York: Academic Press. p. 770. ISBN 978-1-4832-7308-2.
  3. ^ Thétiot-Laurent SA, Boissier J, Robert A, Meunier B (July 2013). "Schistosomiasis chemotherapy". Angewandte Chemie. 52 (31): 7936–7956. doi:10.1002/anie.201208390. PMID 23813602.
  4. ^ DE 919107, Mauss H, "Verfahren zur Herstellung von Xanthenen oder Thioxanthenen.", issued 1954-10-14, assigned to Bayer AG 
  5. ^ Hackmann C, Gönnert R, Mauß H (January 1949). "Untersuchungen über die tumorhemmende Wirkung des Miracils" [Studies on the tumor-inhibiting effect of Miracil]. The Science of Nature (in German). 36 (1): 29–29. doi:10.1007/BF00588669.
  6. ^ Rosi D, Peruzzotti G, Dennis EW, Berberian DA, Freele H, Tullar BF, et al. (September 1967). "Hycanthone, a new active metabolite of lucanthone". Journal of Medicinal Chemistry. 10 (5): 867–876. doi:10.1021/jm00317a025. PMID 4963368.
  7. ^ Berberian DA, Dennis EW, Freele H, Rosi D, Lewis TR, Lorenz R, et al. (July 1969). "Comparison of schistosomicidal activity of xanthenones and 4-methyl-3-chloroanilines and their hydroxymethyl analogs in Swiss mice and Syrian hamsters infected with Schistosoma mansoni". Journal of Medicinal Chemistry. 12 (4): 607–610. doi:10.1021/jm00304a010. PMID 5793149.
  8. ^ Shekhar KC (September 1991). "Schistosomiasis drug therapy and treatment considerations". Drugs. 42 (3): 379–405. doi:10.2165/00003495-199142030-00004. PMID 1720380.
  9. ^ Hillman GR, Senft AW (September 1975). "Anticholinergic properties of the antischistosomal drug hycanthone". The American Journal of Tropical Medicine and Hygiene. 24 (5): 827–834. doi:10.4269/ajtmh.1975.24.827. PMID 1190369.
  10. ^ Alpatov VV (1950). "Biochemical Resemblance Between Endoparasites and Malignant Tumors" (PDF). Priroda. 39 (10): 22–27 – via Electronic Reading Room, U.S. Central Intelligence Agency.
  11. ^ Hirschberg E, Gellhorn A, Murray MR, Elslager EF (March 1959). "Effects of miracil D, amodiaquin, and a series of other 10-thiaxanthenones and 4-aminoquinolines against a variety of experimental tumors in vitro and in vivo". Journal of the National Cancer Institute. 22 (3): 567–579. PMID 13642019.
  12. ^ Hirschberg E, Weinstein IB, Gersten N, Marner E, Finkelstein T, Carchman R (March 1968). "Structure-activity studies on the mechanism of action of miracil D". Cancer Research. 28 (3): 601–607. PMID 4966649.
  13. ^ Turner S, Bases R, Pearlman A, Nobler M, Kabakow B (March 1975). "The adjuvant effect of lucanthone (miracil D) in clinical radiation therapy". Radiology. 114 (3): 729–731. doi:10.1148/114.3.729. PMID 1118579.
  14. ^ Reztsova VV, Goriukhina TA, Seĭts IF (1978). "[Molecular mechanism of the antitumor action of lucanthone]". Voprosy Onkologii. 24 (1): 91–94. PMID 205049.
  15. ^ Archer S, Zayed AH, Rej R, Rugino TA (September 1983). "Analogues of hycanthone and lucanthone as antitumor agents". Journal of Medicinal Chemistry. 26 (9): 1240–1246. doi:10.1021/jm00363a007. PMID 6887199.
  16. ^ Del Rowe JD, Bello J, Mitnick R, Sood B, Filippi C, Moran J, et al. (January 1999). "Accelerated regression of brain metastases in patients receiving whole brain radiation and the topoisomerase II inhibitor, lucanthone". International Journal of Radiation Oncology, Biology, Physics. 43 (1): 89–93. doi:10.1016/s0360-3016(98)00374-5. PMID 9989518.
  17. ^ Carew JS, Kelly KR, Nawrocki ST (2012). "Autophagy as a target for cancer therapy: new developments". Cancer Management and Research. 4: 357–365. doi:10.2147/CMAR.S26133. PMC 3474143. PMID 23091399.
  18. ^ Radin DP, Smith G, Moushiaveshi V, Wolf A, Bases R, Tsirka SE (2022). "Lucanthone Targets Lysosomes to Perturb Glioma Proliferation, Chemoresistance and Stemness, and Slows Tumor Growth In Vivo". Frontiers in Oncology. 12 852940. doi:10.3389/fonc.2022.852940. PMC 9048484. PMID 35494072.
  19. ^ Radin DP, Shifman S, Outhwaite IR, Sharma A, Bases R, Seeliger MA, et al. (March 2024). "Lucanthone, a Potential PPT1 Inhibitor, Perturbs Stemness, Reduces Tumor Microtube Formation, and Slows the Growth of Temozolomide-Resistant Gliomas In Vivo". The Journal of Pharmacology and Experimental Therapeutics. 389 (1): 51–60. doi:10.1124/jpet.123.002021. PMC 10949164. PMID 38296645.
  20. ^ Zhang R, Wang Y, Bai L, Guo X, Jing J, Jia J, et al. (2025). "Lucanthone inhibits the proliferation of lung cancer cells by suppressing the cuproptosis-related pathway". American Journal of Cancer Research. 15 (11): 4857–4884. doi:10.62347/TVGD6582. PMC 12696536. PMID 41395284.
  21. ^ Mauss H (1948). "Über basisch substituierte Xanthon- und Thioxanthon-Abkömmlinge; Miracil, ein neues Chemotherapeuticum". Chemische Berichte. 81: 19–31. doi:10.1002/cber.19480810104.
  22. ^ Archer S, Suter CM (1952). "The Preparation of Some 1-Alkylamino- and Dialkylaminoalkylaminothiaxanthones1". Journal of the American Chemical Society. 74 (17): 4296–4309. doi:10.1021/ja01137a017.
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