Vitamin D has a well-known role in the calcium homeostasis associated with the maintenance of healthy bones. It increases the efficiency of the intestinal absorption of dietary calcium, reduces calcium losses in urine, and mobilizes calcium stored in the skeleton. However, vitamin D receptors are present ubiquitously in the human body and indeed, vitamin D has a plethora of non-calcemic functions. In contrast to most vitamins, sufficient vitamin D can be synthesized in human skin. However, its production can be markedly decreased due to factors such as clothing, sunscreens, intentional avoidance of the direct sunlight, or the high latitude of the residence. Indeed, more than one billion people worldwide are vitamin D deficient, and the deficiency is frequently undiagnosed. The chronic deficiency is not only associated with rickets/osteomalacia/osteoporosis but it is also linked to a higher risk of hypertension, type 1 diabetes, multiple sclerosis, or cancer. Supplementation of vitamin D may be hence beneficial, but the intake of vitamin D should be under the supervision of health professionals because overdosing leads to intoxication with severe health consequences. For monitoring vitamin D, several analytical methods are employed, and their advantages and disadvantages are discussed in detail in this review.

• Klíčová slova
• Calcitriol, calcium, cholecalciferol, detection, ergocalciferol, immunity, rickets,
• MeSH
• lidé MeSH
• nedostatek vitaminu D * komplikace   farmakoterapie   MeSH
• rachitida * komplikace   farmakoterapie   MeSH
• vápník dietní MeSH
• vápník MeSH
• vitamin D metabolismus   terapeutické užití   MeSH
• vitaminy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• vápník dietní MeSH
• vápník MeSH
• vitamin D MeSH
• vitaminy MeSH

Flavonoids are considered beneficial, but they may exhibit pro-oxidative effects likely due to metal reducing properties. For the first time, 24 structurally related flavonoids were compared for copper reduction, and modulation of the copper-triggered Fenton reaction and lysis of erythrocytes. The vast majority of flavonoids reduced cupric ions; their behaviour ranged from progressive gradual reduction through bell-shaped, neutral, to a blockade of spontaneous reduction. Similarly, different behaviours were observed with the Fenton reaction. Flavone was the only flavonoid that potentiated copper-triggered haemolysis (155 ± 81 % at twice the amount of Cu2+), while 18 flavonoids were at least partly protective in some concentrations. Only 5-hydroxyflavone did not reduce Cu2+ and behaved as an antioxidant in both assays (reduction of 60 ± 10 % and 88 ± 1%, respectively, at an equimolar ratio with Cu2+). In conclusion, relatively subtle structural differences resulted in very different anti/prooxidant behaviour depending on the model.

• Klíčová slova
• Antioxidants, Copper, Fenton reaction, Flavonoids, Hydroxyl radical, Reduction,
• MeSH
• antioxidancia chemie   MeSH
• flavonoidy * chemie   MeSH
• hemolýza MeSH
• ionty MeSH
• lidé MeSH
• měď * chemie   MeSH
• oxidace-redukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• flavonoidy * MeSH
• ionty MeSH
• měď * MeSH

Data on alkaloid interactions with the physiologically important transition metals, iron and copper, are mostly lacking in the literature. However, these interactions can have important consequences in the treatment of both Alzheimer's disease and cancer. As isoquinoline alkaloids include galanthamine, an approved drug for Alzheimer's disease, as well as some potentially useful compounds with cytostatic potential, 28 members from this category of alkaloids were selected for a complex screening of interactions with iron and copper at four pathophysiologically relevant pH and in non-buffered conditions (dimethyl sulfoxide) by spectrophotometric methods in vitro. With the exception of the salts, all the alkaloids were able to chelate ferrous and ferric ions in non-buffered conditions, but only five of them (galanthine, glaucine, corydine, corydaline and tetrahydropalmatine) evoked some significant chelation at pH 7.5 and only the first two were also active at pH 6.8. By contrast, none of the tested alkaloids chelated cuprous or cupric ions. All the alkaloids, with the exception of the protopines, significantly reduced the ferric and cupric ions, with stronger effects on the latter. These effects were mostly dependent on the number of free aromatic hydroxyls, but not other hydroxyl groups. The most potent reductant was boldine. As most of the alkaloids chelated and reduced the ferric ions, additional experimental studies are needed to elucidate the biological relevance of these results, as chelation is expected to block reactive oxygen species formation, while reduction could have the opposite effect.

• Klíčová slova
• alkaloid, chelation, copper, iron, reduction,
• MeSH
• Alzheimerova nemoc * MeSH
• chelátory chemie   MeSH
• cytostatické látky * MeSH
• dimethylsulfoxid MeSH
• galantamin MeSH
• hydroxylový radikál MeSH
• isochinoliny farmakologie   MeSH
• lidé MeSH
• měď chemie   MeSH
• reaktivní formy kyslíku MeSH
• redukční činidla MeSH
• soli MeSH
• železo chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chelátory MeSH
• cytostatické látky * MeSH
• dimethylsulfoxid MeSH
• galantamin MeSH
• hydroxylový radikál MeSH
• isochinoliny MeSH
• měď MeSH
• reaktivní formy kyslíku MeSH
• redukční činidla MeSH
• soli MeSH
• železo MeSH

Isoquinoline alkaloids have multiple biological activities, which might be associated with positive pharmacological effects as well as negative adverse reactions. As bleeding was suggested to be a side effect of the isoquinoline alkaloid berberine, we decided to ascertain if different isoquinoline alkaloids could influence hemocoagulation through the inhibition of either platelet aggregation or blood coagulation. Initially, a total of 14 compounds were screened for antiplatelet activity in whole human blood by impedance aggregometry. Eight of them demonstrated an antiplatelet effect against arachidonic acid-induced aggregation. Papaverine and bulbocapnine were the most potent compounds with biologically relevant IC50 values of 26.9 ± 12.2 μM and 30.7 ± 5.4 μM, respectively. Further testing with the same approach confirmed their antiplatelet effects by employing the most physiologically relevant inducer of platelet aggregation, collagen, and demonstrated that bulbocapnine acted at the level of thromboxane receptors. None of the alkaloids tested had an effect on blood coagulation measured by a mechanical coagulometer. In conclusion, the observed antiplatelet effects of isoquinoline alkaloids were found mostly at quite high concentrations, which means that their clinical impact is most likely low. Bulbocapnine was an exception. It proved to be a promising antiplatelet molecule, which may have biologically relevant effects.

• Klíčová slova
• antiplatelet, bleeding, bulbocapnine, drug, isoquinoline,
• MeSH
• agregace trombocytů * MeSH
• alkaloidy * farmakologie   MeSH
• inhibitory agregace trombocytů farmakologie   MeSH
• isochinoliny farmakologie   MeSH
• lidé MeSH
• trombocyty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkaloidy * MeSH
• inhibitory agregace trombocytů MeSH
• isochinoliny MeSH

OBJECTIVES: Both pyridine and pyrano derivatives have been previously shown to possess biologically relevant activity. In this study, we report the incorporation of these two scaffolds into one molecule. METHODS: The designed 3,3-dimethyl-6-oxopyrano[3,4-c]pyridines were synthesized by the acylation of enamine under Stork conditions followed by condensation of formed β-diketones with 2-cyanoacetamide. The structures of these compounds were confirmed by using a wide spectrum of physico-chemical methods. Their antiplatelet, anticoagulant and vasodilatory activity together with toxicity were evaluated. KEY FINDINGS: A series of 6-oxopyrano[3,4-c]pyridines 3a-j was obtained. Four of these compounds were reported for the first time. None of the tested compounds demonstrated anticoagulant effect but 8-methyl derivative (3a) was a potent antiplatelet compound with IC50 numerically twice as low as the clinically used acetylsalicylic acid. A series of further mechanistic tests showed that 3a interferes with calcium signaling. The compound is also not toxic and in addition possesses vasodilatory activity as well. CONCLUSIONS: Compound 3a is a promising inhibitor of platelet aggregation, whose mechanism of action should be studied in detail.

• Klíčová slova
• anticoagulant, antiplatelet activity, cytotoxicity, pyranopyridine, vasodilatory, β-diketones,
• MeSH
• agregace trombocytů * MeSH
• antikoagulancia farmakologie   MeSH
• inhibitory agregace trombocytů * chemie   farmakologie   MeSH
• pyridiny farmakologie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antikoagulancia MeSH
• inhibitory agregace trombocytů * MeSH
• pyridiny MeSH

BACKGROUND: Antiplatelet drugs represent the keystone in the treatment and prevention of diseases of ischemic origin, including coronary artery disease. The current palette of drugs represents efficient modalities in most cases, but their effect can be limited in certain situations or associated with specific side effects. In this study, representatives of compounds selected from series having scaffolds with known or potential antiplatelet activity were tested. These compounds were previously synthetized by us, but their biological effects have not yet been reported. OBJECTIVE: The aim of this study was to examine the antiplatelet and anticoagulation properties of selected compounds and determine their mechanism of action. METHODS: Antiplatelet activity of compounds and their mechanisms of action were evaluated using human blood by impedance aggregometry and various aggregation inducers and inhibitors and compared to appropriate standards. Cytotoxicity was tested using breast adenocarcinoma cell cultures and potential anticoagulation activity was also determined. RESULTS: In total, four of 34 compounds tested were equally or more active than the standard antiplatelet drug Acetylsalicylic Acid (ASA). In contrast to ASA, all 4 active compounds decreased platelet aggregation triggered not only by collagen, but also partly by ADP. The major mechanism of action is based on antagonism at thromboxane receptors. In higher concentrations, inhibition of thromboxane synthase was also noted. In contrast to ASA, the tested compounds did not block cyclooxygenase- 1. CONCLUSION: The most active compound, 2-amino-4-(1H-indol-3-yl)-6-nitro-4H-chromene-3- carbonitrile (2-N), which is 4-5x times more potent than ASA, is a promising compound for the development of novel antiplatelet drugs.

• Klíčová slova
• Pyridopyrimidine, acridine, aggregation, coagulation, coumarin, indole,
• MeSH
• agregace trombocytů MeSH
• Aspirin farmakologie   MeSH
• heterocyklické sloučeniny * farmakologie   MeSH
• inhibitory agregace trombocytů * farmakologie   MeSH
• lidé MeSH
• trombocyty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Aspirin MeSH
• heterocyklické sloučeniny * MeSH
• inhibitory agregace trombocytů * MeSH

Vitamin K is traditionally connected with blood coagulation, since it is needed for the posttranslational modification of 7 proteins involved in this cascade. However, it is also involved in the maturation of another 11 or 12 proteins that play different roles, encompassing in particular the modulation of the calcification of connective tissues. Since this process is physiologically needed in bones, but is pathological in arteries, a great deal of research has been devoted to finding a possible link between vitamin K and the prevention of osteoporosis and cardiovascular diseases. Unfortunately, the current knowledge does not allow us to make a decisive conclusion about such a link. One possible explanation for this is the diversity of the biological activity of vitamin K, which is not a single compound but a general term covering natural plant and animal forms of vitamin K (K1 and K2) as well as their synthetic congeners (K3 and K4). Vitamin K1 (phylloquinone) is found in several vegetables. Menaquinones (MK4-MK13, a series of compounds known as vitamin K2) are mostly of a bacterial origin and are introduced into the human diet mainly through fermented cheeses. Current knowledge about the kinetics of different forms of vitamin K, their detection, and their toxicity are discussed in this review.

• Klíčová slova
• bioanalysis, coagulation, diet, menaquinone, phylloquinone,
• MeSH
• kinetika MeSH
• lidé MeSH
• osteoporóza * MeSH
• vitamin K 1 MeSH
• vitamin K 2 MeSH
• vitamin K * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• vitamin K 1 MeSH
• vitamin K 2 MeSH
• vitamin K * MeSH

This review summarizes the current knowledge on essential vitamins B1, B2, B3, and B5. These B-complex vitamins must be taken from diet, with the exception of vitamin B3, that can also be synthetized from amino acid tryptophan. All of these vitamins are water soluble, which determines their main properties, namely: they are partly lost when food is washed or boiled since they migrate to the water; the requirement of membrane transporters for their permeation into the cells; and their safety since any excess is rapidly eliminated via the kidney. The therapeutic use of B-complex vitamins is mostly limited to hypovitaminoses or similar conditions, but, as they are generally very safe, they have also been examined in other pathological conditions. Nicotinic acid, a form of vitamin B3, is the only exception because it is a known hypolipidemic agent in gram doses. The article also sums up: (i) the current methods for detection of the vitamins of the B-complex in biological fluids; (ii) the food and other sources of these vitamins including the effect of common processing and storage methods on their content; and (iii) their physiological function.

• Klíčová slova
• essential, niacin, pantothenic acid, riboflavin, thiamine,
• MeSH
• avitaminóza * MeSH
• lidé MeSH
• thiamin MeSH
• vitamin A MeSH
• vitamin B komplex * MeSH
• vitamin K MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• thiamin MeSH
• vitamin A MeSH
• vitamin B komplex * MeSH
• vitamin K MeSH

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 IC50 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.

• Klíčová slova
• 4-methylcatechol, aggregation, catechol, flavonoid, platelet, whole blood,
• MeSH
• agregace trombocytů * MeSH
• fenol * MeSH
• fenoly farmakologie   MeSH
• inhibitory agregace trombocytů farmakologie   MeSH
• lidé MeSH
• trombin farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fenol * MeSH
• fenoly MeSH
• inhibitory agregace trombocytů MeSH
• trombin MeSH

Quercetin, a common flavonoid from human diet, is extensively metabolized. Its two metabolites with the preserved flavonoid core were tested in detail for their interactions with transition metals, iron and copper. Both compounds chelated both metals; however, there were some significant differences between them notwithstanding that the major chelation site (3-hydroxy-4-keto) was the same. The complex stoichiometries were also determined under different pH conditions and in both oxidation states. Mostly, complexes 2:1, flavonoid to metal, were observed. Both compounds reduced iron and copper in a bell-shaped manner with tamarixetin being less potent in general. Both metabolites potentiated the Fenton reaction triggered by iron, while they were able to decrease the copper-based Fenton reaction under acidic conditions. In cellular experiments, both metabolites attenuated the copper-triggered hemolysis with isorhamnetin being more potent. In conclusion, there are differences between methylated metabolites of quercetin in relation to their interactions with biologically relevant transition metals.

• Klíčová slova
• antioxidant, chelator, hemolysis, pro-oxidant, reduction, stoichiometry,
• MeSH
• disacharidy MeSH
• lidé MeSH
• měď * MeSH
• quercetin * analogy a deriváty   MeSH
• železo MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 3-methylquercetin MeSH Prohlížeč
• disacharidy MeSH
• měď * MeSH
• quercetin * MeSH
• tamarixetin MeSH Prohlížeč
• železo MeSH