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Clionasterol: A Potent Inhibitor of Complement Component C1
Abstract
Clionasterol (1a), clionasterol monoacetate (1b) and 5alpha,8alpha-epidioxy-24alpha-ethylcholest-6-en-3-ol (2), isolated from the marine sponge Xestospongia exigua, and beta-sitosterol (3) were tested for their influence on the classical (CP) and alternative (AP) pathways of activation of the human complement system in vitro. All the sterols inhibited the CP in a dose-dependent manner but no detectable effect was observed in the AP even at concentrations of 400 microM. Clionasterol was found to be a potent inhibitor of CP (IC50 = 4.1 microM) being ten-fold more active than beta-sitosterol. The presence of the epidioxy group on C-5 and C-8 of compound 2 caused a pronounced decrease of the inhibitory effect. Mechanistic studies on the anticomplementary effect of clionasterol revealed that it interferes with the complement component C1.
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Gamma-sitosterol is known for anti-diabetic activities and is a potent inhibitor of complement C1 component.
“First, gamma sitosterol (steroid) was known for its anti diabetic activities32 and known potent inhibitor of complement C1 component33.”
From Bioactivities of Allium longicuspis Regel against anthracnose of mango caused by Colletotrichum gloeosporioides (Penz.) (2020) · cites this paper as [33]
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Metadata
- Authors
- Cerqueira, F., Watanadilok, R., Sonchaeng, P., Kijjoa, A., Pinto, M., Quarles van Ufford, H., Kroes, B., Beukelman, C., & Nascimento, M. S.
- Affiliations
- Universidade do Porto (PT)
- Burapha University (TH)
- Utrecht University (NL)
- Venue
- Planta Medica
- Publisher
- Georg Thieme Verlag KG
- Published
- 2003-02
- Volume
- 69
- Issue
- 2
- Pages
- 174-176
- ISSN
- 0032-0943 (ISSN-L)
- 1439-0221
- OpenAlex
- W2031203393
- Cited by
- 27
- References
- 0
- Citations by year
- 2024: 4 · 2023: 5 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 1 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 1
- FWCI
- 0.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Planta Medica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundação para a Ciência e a Tecnologia
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Marine Sponges and Natural Products
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Physical Sciences › Chemistry › Organic Chemistry › Natural product bioactivities and synthesis
- Keywords
- clionasterol, complement system, classical complement pathway, alternative complement pathway, marine sponge natural products, sterols, β-sitosterol, structure-activity relationship, anticomplementary activity
- MeSH terms
- Animals, Complement Inactivator Proteins, Complement Pathway, Alternative, Complement Pathway, Classical, Dose-Response Relationship, Drug, Hemolysis, Humans, Porifera, Sitosterols, Inhibitory Concentration 50
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