Canthin-6-Ones: Potential Drugs for Chronic Inflammatory Diseases by Targeting Multiple Inflammatory Mediators
Abstract
:1. Introduction
2. Unchecked Inflammation and CID
3. Anti-Inflammatory Effects of Canthin-6-Ones
3.1. Canthin-6-Ones Suppress the Progression of Several CIDs
3.1.1. Inflammatory Bowel Disease (IBD)
3.1.2. Alzheimer’s Disease (AD)
3.1.3. Parkinson’s Disease (PD)
3.1.4. Diabetes Mellitus (DM)
3.1.5. Rheumatoid Arthritis (RA)
3.1.6. Ulcers
3.1.7. Erectile Dysfunction (ED)
3.1.8. Tumors
Compound No. | Compound Name | Source | Study Type | Effective Dose/IC50 | Reference |
---|---|---|---|---|---|
(10) | 9-Hydroxycanthin-6-one | Eurycoma longifolia | In vitro | Suppressed the proliferation of a melanoma cell line (5.4 μM) | [52] |
(11) | 4,5-Dimethoxy-10-hydroxycanthin-6-one | Picrasma quassioides (D. Don) Benn | In vitro | Suppressed the proliferation of CNE2 (11.6 ± 2.48 μM) and Bel-7402 (118.91 ± 67.42μM) cell lines | [47] |
(12) | 4,5-Dimethoxy- canthin-6-one | Picrasma quassioides Benn (Simarobaceae) | In vitro | Suppressed the proliferation of CNE2 (9.86 ± 1.49 μM) and Bel-7402 (32.27 ± 9.74 μM) cell lines | [47] |
(14) | 9-Methoxycanthin-6-one | Eurycoma longifolia | In vitro | Suppressed the proliferation of A2780 (4.04 ± 0.36 μM), SKOV-3 (5.80 ± 0.40 μM), MCF-7 (15.09 ± 0.99 μM), HT-29 (3.79 ± 0.069 μM), A375 (5.71 ± 0.20 μM), and HeLa (4.30 ± 0.27 μM) cell lines | [29,93] |
(15) | 6-Hydroxy-4-methoxy canthin-6-one | Picrasma quassioides BENN | In vitro | Suppressed the proliferation of CT26.WT, K-562, SGC-7901, Hep G2, and A-549 cell lines (>50 μM) | [47,102] |
(16) | 9-Methoxycanthin-6-one-N-oxide | Eurycoma longifolia | In vitro | Suppressed the proliferation of a melanoma cell line (6.5 μM) | [52,93] |
(17) | 9-Hydroxycanthin-6-one-N-oxide | Eurycoma longifolia | In vitro | Suppressed the proliferation of a melanoma cell line (7.0 μM) | [52] |
(18) | 8-Hydroxycanthin-6-one | Picrasma quassioides (D. Don) Benn | In vitro | Suppressed the proliferation of CNE2(13.43 ± 2.29 μM) and Bel-7402(39.27 ± 9.72 μM) cell lines | [47] |
(19) | 1-Methoxy-canthin-6-one | Ailanthus altissima Swingle | In vitro | Suppressed the proliferation of thyroid carcinoma and hepatocellular carcinoma cell lines (40 μM). | [103] |
(20) | 1,11-Dimethoxycanthin-6-one | Brucea antidysentrica | In silico | Showed consecutive binding affinity with mainly hydrophobic interaction (−11.0 kcal/mol) | [94] |
(21) | 2-Methoxycanthin-6-one | Brucea antidysentrica | In silico | Showed consecutive binding affinity with mainly hydrophobic interaction (−11.9 kcal/mol) | [94] |
(22) | 10-Methoxycanthin-6-one | Chemical synthesis | In vitro | Suppressed the proliferation of Kasumi-1 (80μM) and KG-1 (36μM) | [95] |
3.2. Mechanism of Action and Pathways for Canthin-6-Ones
3.2.1. NF-κB Pathway
3.2.2. MAPK Pathway
3.2.3. JAK/STAT Pathway
3.2.4. PI3K–AKT Pathway
3.3. Major Inflammatory Mediators Regulated by Canthin-6-Ones
3.3.1. Pro-Inflammatory Cytokines
3.3.2. NO
3.3.3. PGE2
4. Structure–Activity Relationships of Canthin-6-Ones
5. Limitations and Possible Solutions
6. Conclusions and Perspectives
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Compound No. | Compound Name | Source | Study Type | Effects on Disease Models | Effects on Inflammatory Pathways | Reference |
---|---|---|---|---|---|---|
(1) | Canthin-6-one | Several plants, including the initial source, Pentaceras australis | In vivo /In vitro | Suppresses colitis model in Wistar rats by oral gavage (1, 5, and 25 mg/kg) | Suppresses the expression of NO and COX2 (12.5, 25, and 50 μM), PDE-5 (4.31 ± 0.52 μM), NF-κB, MAPK, STAT3, PI3K/Akt, and the NLRP3 inflammasome (6.5, 12.5, and 25 μM) | [15,17,25,27,29,40,45] |
(2) | 10-Hydroxycanthin-6-one | Chemical synthesis | In vitro | Unknown | Suppresses the expression of NO (5.92 ± 0.9~15.09 ± 1.8 μM) | [45,46] |
(3) | 3-Methylcanthin-5,6-dione | Picrasma quassioides (D. Don) Benn | In vivo /In vitro | Suppresses Alzheimer’s disease model in ICR mice by oral administration (25, 50, 100 mg/kg) | Suppresses the expression of NO (3~30 μM) | [12,47,48,49] |
(4) | 1:4-Methoxy-5-hyroxycanthin-6-one | Picrasma quassiodes (D. Don) Benn. | In vivo | Suppresses artery hypertension disease model in spontaneously hypertensive rats by oral gavage. Suppresses the expression of NO (50, 100, 200 mg/kg) | Unknown | [50] |
(5) | 11-Hydroxycanthin-6-one | Brucea mollis var. tonkinensis | In vitro | Unknown | Suppresses the expression of NO (5.92 ± 0.9~15.09 ± 1.8 μM) | [45,51] |
(6) | 4-Methoxy-5hydroxy-canthin-6-one | Picrasma quassioides | In vivo/In vitro | Suppresses chronic arthritis model in male Sprague–Dawley (SD) rats by oral administration (3, 9, 27 mg/kg) | Suppresses the expression of NO (10, 30, and 100 μM) | [15] |
(7) | (R)-5-(1-hydroxyethyl)-canthin-6-one | Ailanthus altissima Swingle | In vitro | Unknown | Suppresses the expression of NO (5.92 ± 0.9~15.09 ± 1.8 μM) | [45] |
(8) | 9-Methoxy-canthin-6-one | Simaroubaceae plants | In vitro | Unknown | Suppresses the expression of NO and COX2 (12.5, 25, and 50 μM) or the activity of PDE-5 (3.30 ± 1.03 μM) | [15,17,26,29] |
(9) | 5-(1-Hydroxyethyl)- 6-canthin-6-one | Ailanthus altissima | In vitro | Unknown | Suppresses NF-κB pathway (15 μM) | [27] |
(10) | 9-Hydroxycanthin-6-one | Eurycoma longifolia | In vivo /In vitro | Suppresses Alzheimer disease model in mice by oral administration (25, 50, 100 mg/kg) | Suppresses NF-κB pathway (3.8 μM) and the activity of PDE-5 (4.66 ± 1.13 μM) | [12,17,26,45,52] |
(11) | 4,5-Dimethoxy-10-hydroxycanthin-6-one | Picrasma quassioides (D. Don) Benn | In vivo/In vitro | Suppresses Alzheimer disease model in mice by oral administration (25, 50, 100 mg/kg) | Suppresses the expression of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α (25 μM, 50 μM, and 100 μM) | [12] |
(12) | 4,5-Dimethoxy- canthin-6-one | Picrasma quassioides BENNET | In vivo/In vitro | Suppresses Alzheimer disease model in mice by oral administration (25, 50, 100 mg/kg) | Suppresses the expression of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α (25 μM, 50 μM, and 100 μM) | [12] |
(13) | 4-Methoxy-5-hydroxyl- 5-canthin-6-one | Picrasma quassioides BENNET | In vivo/In vitro | Suppresses Alzheimer disease model in mice by oral administration (25, 50, 100 mg/kg) | Suppresses the expression of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α (25 μM, 50 μM, and 100 μM) | [12] |
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Zhang, Z.; Wang, A.; Wang, Y.; Sun, W.; Zhou, X.; Xu, Q.; Mao, L.; Zhang, J. Canthin-6-Ones: Potential Drugs for Chronic Inflammatory Diseases by Targeting Multiple Inflammatory Mediators. Molecules 2023, 28, 3381. https://doi.org/10.3390/molecules28083381
Zhang Z, Wang A, Wang Y, Sun W, Zhou X, Xu Q, Mao L, Zhang J. Canthin-6-Ones: Potential Drugs for Chronic Inflammatory Diseases by Targeting Multiple Inflammatory Mediators. Molecules. 2023; 28(8):3381. https://doi.org/10.3390/molecules28083381
Chicago/Turabian StyleZhang, Zongying, Anqi Wang, Yunhan Wang, Weichen Sun, Xiaorong Zhou, Qiuyun Xu, Liming Mao, and Jie Zhang. 2023. "Canthin-6-Ones: Potential Drugs for Chronic Inflammatory Diseases by Targeting Multiple Inflammatory Mediators" Molecules 28, no. 8: 3381. https://doi.org/10.3390/molecules28083381