Comparison of Antiplatelet Effects of Phenol Derivatives in Humans
Flavonoids are associated with positive cardiovascular effects. However, due to their low bioavailability, metabolites are likely responsible for these properties. Recently, one of these metabolites, 4-methylcatechol, was described to be a very potent antiplatelet compound. This study aimed to compa...
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MDPI AG
2022-01-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/1/117 |
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| author | Marcel Hrubša Raúl Alva Mst Shamima Parvin Kateřina Macáková Jana Karlíčková Jaka Fadraersada Lukáš Konečný Monika Moravcová Alejandro Carazo Přemysl Mladěnka |
| author_facet | Marcel Hrubša Raúl Alva Mst Shamima Parvin Kateřina Macáková Jana Karlíčková Jaka Fadraersada Lukáš Konečný Monika Moravcová Alejandro Carazo Přemysl Mladěnka |
| author_sort | Marcel Hrubša |
| collection | DOAJ |
| description | Flavonoids are associated with positive cardiovascular effects. However, due to their low bioavailability, metabolites are likely responsible for these properties. Recently, one of these metabolites, 4-methylcatechol, was described to be a very potent antiplatelet compound. This study aimed to compare its activity with its 22 close derivatives both of natural or synthetic origin in order to elucidate a potential structure–antiplatelet activity relationship. Blood from human volunteers was induced to aggregate by arachidonic acid (AA), collagen or thrombin, and plasma coagulation was also studied. Potential toxicity was tested on human erythrocytes as well as on a cancer cell line. Our results indicated that 17 out of the 22 compounds were very active at a concentration of 40 μM and, importantly, seven of them had an IC<sub>50</sub> on AA-triggered aggregation below 3 μM. The effects of the most active compounds were confirmed on collagen-triggered aggregation too. None of the tested compounds was toxic toward erythrocytes at 50 μM and four compounds partly inhibited proliferation of breast cancer cell line at 100 μM but not at 10 μM. Additionally, none of the compounds had a significant effect on blood coagulation or thrombin-triggered aggregation. This study hence reports four phenol derivatives (4-ethylcatechol, 4-fluorocatechol, 2-methoxy-4-ethylphenol and 3-methylcatechol) suitable for future in vivo testing. |
| first_indexed | 2024-03-10T01:50:00Z |
| format | Article |
| id | doaj.art-60172e55a63f4923982ab2576e429a7d |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T01:50:00Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-60172e55a63f4923982ab2576e429a7d2023-11-23T13:07:19ZengMDPI AGBiomolecules2218-273X2022-01-0112111710.3390/biom12010117Comparison of Antiplatelet Effects of Phenol Derivatives in HumansMarcel Hrubša0Raúl Alva1Mst Shamima Parvin2Kateřina Macáková3Jana Karlíčková4Jaka Fadraersada5Lukáš Konečný6Monika Moravcová7Alejandro Carazo8Přemysl Mladěnka9Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech RepublicDepartment of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech RepublicDepartment of Pharmacognosy, Faculty of Pharmacy, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech RepublicDepartment of Pharmacognosy, Faculty of Pharmacy, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech RepublicDepartment of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech RepublicDepartment of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech RepublicDepartment of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech RepublicDepartment of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech RepublicDepartment of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech RepublicDepartment of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech RepublicFlavonoids are associated with positive cardiovascular effects. However, due to their low bioavailability, metabolites are likely responsible for these properties. Recently, one of these metabolites, 4-methylcatechol, was described to be a very potent antiplatelet compound. This study aimed to compare its activity with its 22 close derivatives both of natural or synthetic origin in order to elucidate a potential structure–antiplatelet activity relationship. Blood from human volunteers was induced to aggregate by arachidonic acid (AA), collagen or thrombin, and plasma coagulation was also studied. Potential toxicity was tested on human erythrocytes as well as on a cancer cell line. Our results indicated that 17 out of the 22 compounds were very active at a concentration of 40 μM and, importantly, seven of them had an IC<sub>50</sub> on AA-triggered aggregation below 3 μM. The effects of the most active compounds were confirmed on collagen-triggered aggregation too. None of the tested compounds was toxic toward erythrocytes at 50 μM and four compounds partly inhibited proliferation of breast cancer cell line at 100 μM but not at 10 μM. Additionally, none of the compounds had a significant effect on blood coagulation or thrombin-triggered aggregation. This study hence reports four phenol derivatives (4-ethylcatechol, 4-fluorocatechol, 2-methoxy-4-ethylphenol and 3-methylcatechol) suitable for future in vivo testing.https://www.mdpi.com/2218-273X/12/1/117platelet4-methylcatecholflavonoidaggregationwhole bloodcatechol |
| spellingShingle | Marcel Hrubša Raúl Alva Mst Shamima Parvin Kateřina Macáková Jana Karlíčková Jaka Fadraersada Lukáš Konečný Monika Moravcová Alejandro Carazo Přemysl Mladěnka Comparison of Antiplatelet Effects of Phenol Derivatives in Humans Biomolecules platelet 4-methylcatechol flavonoid aggregation whole blood catechol |
| title | Comparison of Antiplatelet Effects of Phenol Derivatives in Humans |
| title_full | Comparison of Antiplatelet Effects of Phenol Derivatives in Humans |
| title_fullStr | Comparison of Antiplatelet Effects of Phenol Derivatives in Humans |
| title_full_unstemmed | Comparison of Antiplatelet Effects of Phenol Derivatives in Humans |
| title_short | Comparison of Antiplatelet Effects of Phenol Derivatives in Humans |
| title_sort | comparison of antiplatelet effects of phenol derivatives in humans |
| topic | platelet 4-methylcatechol flavonoid aggregation whole blood catechol |
| url | https://www.mdpi.com/2218-273X/12/1/117 |
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