title: Synthetic analogues of flavonoids with improved activity against platelet activation and aggregation as novel prototypes of food supplements.
abstract: We investigated the ability of quercetin and apigenin to modulate platelet activation and aggregation, and compared the observed efficacy with that displayed by their synthetic analogues 2-phenyl-4H-pyrido[1,2-a]pyrimidin-4-ones, 1-4, and 2,3-diphenyl-4H-pyrido[1,2-a]pyrimidin-4-ones, 5-7. Platelet aggregation was explored through a spectrophotometric assay on platelet-rich plasma (PRP) treated with the thromboxane A2 mimetic U46619, collagen and thrombin in presence/absence of various bioisosteres of flavonoids (12.5-25-50-100 μM). The platelet density, (mean platelet component, MPC), was measured by the Advia 120 Hematology System as a marker surrogate of platelet activation. The induced P-selectin expression, which reflects platelet degranulation/activation, was quantified by flow cytometry on PRP. Our synthetic compounds modulated significantly both platelet activation and aggregation, thus turning out to be more effective than the analogues quercetin and apigenin when tested at a concentration fully consistent with their use in vivo. Accordingly, they might be used as food supplements to increase the efficacy of natural flavonoids.
authors.affiliation: CNR Institute of Clinical Physiology, Via G. Moruzzi, 1, 56124 Pisa, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Del Turco
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno, 6, 56126 Pisa, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Sartini
authors.affiliation: CNR Institute of Clinical Physiology, Via G. Moruzzi, 1, 56124 Pisa, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Cigni
authors.affiliation: CNR Institute of Clinical Physiology, Via G. Moruzzi, 1, 56124 Pisa, Italy.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Sentieri
authors.affiliation: CNR Institute of Clinical Physiology, Via G. Moruzzi, 1, 56124 Pisa, Italy.
authors.forename: Silverio
authors.initials: S
authors.lastname: Sbrana
authors.affiliation: Fondazione Monasterio, CNR-Regione Toscana, Via G. Moruzzi, 1, 56124 Pisa, Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Battaglia
authors.affiliation: Fondazione Monasterio, CNR-Regione Toscana, Via G. Moruzzi, 1, 56124 Pisa, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Papa
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno, 6, 56126 Pisa, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Da Settimo
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno, 6, 56126 Pisa, Italy; Interdepartmental Research Center "Nutraceuticals and Food for Health", University of Pisa, Via del Borghetto, 80, 56124 Pisa, Italy. Electronic address: concettina.lamotta@farm.unipi.it.
authors.forename: Concettina
authors.initials: C
authors.lastname: La Motta
authors.affiliation: CNR Institute of Clinical Physiology, Via G. Moruzzi, 1, 56124 Pisa, Italy. Electronic address: lapina@ifc.cnr.it.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Basta
mesh_terms: D000328:Adult; D047310:Apigenin / Q000494:pharmacology; D019587:Dietary Supplements; D005260:Female; D005419:Flavonoids / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology; D055815:Young Adult
chemical_list: D005419:Flavonoids; D010975:Platelet Aggregation Inhibitors; D047310:Apigenin; D011794:Quercetin
keywords: 2,3-Diphenyl-4H-pyrido[1,2-a]pyrimidin-4-one derivatives, 5–7 (Chart 1); 2,3-Diphenyl-4H-pyrido[1,2-a]pyrimidin-4-ones; 2-Phenyl-4H-pyrido[1,2-a]pyrimidin-4-one derivatives, 1–4 (Chart 1); 2-Phenyl-4H-pyrido[1,2-a]pyrimidin-4-ones; Apigenin; Apigenin, 5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one (PubChem CID: 5280443); P-selectin expression; Platelet aggregation; Quercetin; Quercetin, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one (PubChem CID: 5280343)