Probucol

Probucol
Clinical data
Pronunciation/ˈproʊbjukɒl/
PROH-bew-kol
Trade namesLorelco
Other names2,6-di-tert-butyl-4-({2-[(3,5-di-tert-butyl-4-hydroxyphenyl)sulfanyl]propan-2-yl}sulfanyl)phenol
AHFS/Drugs.comMicromedex Detailed Consumer Information
MedlinePlusa611037
ATC code
Identifiers
  • 4,4'-[Propane-2,2-diylbis(thio)]bis(2,6-di-tert-butylphenol)
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.041.404 Edit this at Wikidata
Chemical and physical data
FormulaC31H48O2S2
Molar mass516.84 g·mol−1
3D model (JSmol)
  • S(c1cc(c(O)c(c1)C(C)(C)C)C(C)(C)C)C(Sc2cc(c(O)c(c2)C(C)(C)C)C(C)(C)C)(C)C
  • InChI=1S/C31H48O2S2/c1-27(2,3)21-15-19(16-22(25(21)32)28(4,5)6)34-31(13,14)35-20-17-23(29(7,8)9)26(33)24(18-20)30(10,11)12/h15-18,32-33H,1-14H3 checkY
  • Key:FYPMFJGVHOHGLL-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Probucol, sold under the trade name Lorelco among others, is an anti-hyperlipidemic drug[1] initially developed for the treatment of coronary artery disease. Clinical use was discontinued in some countries after it was found that the drug may have the undesired effect of lowering HDL in patients with a previous history of heart disease.[2][3] It may also cause QT interval prolongation.[3][4]

Probucol was originally developed as an industrial antioxidant added to tires to maximize their longevity.[5]

Mechanism of action

Probucol lowers the level of cholesterol in the bloodstream by increasing the rate of LDL catabolism. Additionally, probucol may inhibit cholesterol synthesis and delay cholesterol absorption.[6] Probucol is a powerful antioxidant which inhibits the oxidation of cholesterol in LDLs; this slows the formation of foam cells, which form atherosclerotic plaques.

Probucol has also been shown to inhibit ABCA1-dependent cholesterol transport,[7] which may contribute to its known effect of lowering HDL.[8]

Research

Probucol has been found to have antioxidant and anti-inflammatory properties via several different mechanisms.[9] These properties have led to research into the drug's potential capacity to treat sensorineural hearing loss related to oxidative stress,[9][10] as well as formulations to improve the delivery of the drug into the ear.[10]

After promising test results in mouse models, probucol is under study at Weston Brain Institute of McGill University as a possible aid in delaying the onset of Alzheimer's disease.[citation needed]

References

  1. ^ Yamamoto A (11 December 2008). "A Unique Antilipidemic Drug - Probucol". Journal of Atherosclerosis and Thrombosis. 15 (6): 304–5. doi:10.5551/jat.E621. PMID 19075491. Retrieved 2020-01-29.
  2. ^ Yamashita S, Masuda D, Matsuzawa Y (August 2015). "Did we abandon probucol too soon?". Current Opinion in Lipidology. 26 (4): 304–16. doi:10.1097/MOL.0000000000000199. PMID 26125504. Probucol has been used as a lipid-lowering drug for a long time especially in Japan, although Western countries quitted its use because of the reduction in serum HDL-cholesterol (HDL-C).
  3. ^ a b Yamashita S, Matsuzawa Y (November 2009). "Where are we with probucol: a new life for an old drug?". Atherosclerosis. 207 (1): 16–23. doi:10.1016/j.atherosclerosis.2009.04.002. PMID 19457483.
  4. ^ Mamoshina P, Rodriguez B, Bueno-Orovio A (March 2021). "Toward a broader view of mechanisms of drug cardiotoxicity". Cell Reports. 2 (3): 100216. doi:10.1016/j.xcrm.2021.100216. PMC 7974548. PMID 33763655.
  5. ^ Yamashita S, Masuda D, Matsuzawa Y (February 2021). "New Horizons for Probucol, an Old, Mysterious Drug". Journal of Atherosclerosis and Thrombosis. 28 (2): 100–102. doi:10.5551/jat.ED132. PMC 7957029. PMID 32507832. Probucol was developed as an anti-oxidative compound to prevent the degradation of tire rubber and later applied to reduce serum LDL-C levels in patients with hypercholesterolemia.
  6. ^ "Probucol (Systemic)". Drugs.com. 1998-08-24. Retrieved 2020-01-29.
  7. ^ Favari E, Zanotti I, Zimetti F, Ronda N, Bernini F, Rothblat GH (28 October 2004). "Probucol inhibits ABCA1-mediated cellular lipid efflux". Arterioscler. Thromb. Vasc. Biol. 24 (12): 2345–50. doi:10.1161/01.ATV.0000148706.15947.8a. PMID 15514211.
  8. ^ Miida T, Seino U, Miyazaki O, Hanyu O, Hirayama S, Saito T, Ishikawa Y, Akamatsu S, Nakano T, Katsuyuki N, Okazaki M, Okada M (October 2008). "Probucol markedly reduces HDL phospholipids and elevated prebeta1-HDL without delayed conversion into alpha-migrating HDL: putative role of angiopoietin-like protein 3 in probucol-induced HDL remodeling". Atherosclerosis. 200 (2): 329–35. doi:10.1016/j.atherosclerosis.2007.12.031. PMID 18279878. Retrieved 2020-01-29.
  9. ^ a b Chester J, Johnston E, Walker D, Jones M, Ionescu CM, Wagle SR, Kovacevic B, Brown D, Mikov M, Mooranian A, Al-Salami H (July 2021). "A Review on Recent Advancement on Age-Related Hearing Loss: The Applications of Nanotechnology, Drug Pharmacology, and Biotechnology". Pharmaceutics. 13 (7): 1041. doi:10.3390/pharmaceutics13071041. PMC 8309044. PMID 34371732.
  10. ^ a b Wagle SR, Ionescu CM, Kovacevic B, Jones M, Foster T, Lim P, Lewkowicz M, Ðanić M, Mikov M, Mooranian A, Al-Salami H (May 2023). "Pharmaceutical characterization of probucol bile acid-lithocholic acid nanoparticles to prevent chronic hearing related and similar cellular oxidative stress pathologies". Nanomedicine. 18 (12): 923–940. doi:10.2217/nnm-2023-0092. PMID 37529927.