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Govindasamy Mugesh - One of the best experts on this subject based on the ideXlab platform.
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Dehalogenation of Halogenated Nucleobases and Nucleosides by Organoselenium compounds.
Chemistry: A European Journal, 2019Co-Authors: Santanu Mondal, Govindasamy MugeshAbstract:: Halogenated nucleosides, such as 5-iodo-2'-deoxyuridine and 5-iodo-2'-deoxycytidine, are incorporated into the DNA of replicating cells to facilitate DNA single-strand breaks and intra- or interstrand crosslinks upon UV irradiation. In this work, it is shown that the naphthyl-based Organoselenium compounds can mediate the dehalogenation of halogenated pyrimidine-based nucleosides, such as 5-X-2'-deoxyuridine and 5-X-2'-deoxycytidine (X=Br or I). The rate of deiodination was found to be significantly higher than that of the debromination for both nucleosides. Furthermore, the deiodination of iodo-cytidines was found to be faster than that of iodo-uridines. The initial rates of the deiodinations of 5-iodocytosine and 5-iodouracil indicated that the nature of the sugar moiety influences the kinetics of the deiodination. For both the nucleobases and nucleosides, the deiodination and debromination reactions follow a halogen-bond-mediated and addition/elimination pathway, respectively.
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Horseradish peroxidase inhibition and antioxidant activity of ebselen and related Organoselenium compounds.
Bioorganic & medicinal chemistry letters, 2006Co-Authors: B. Mishra, K.i. Priyadarsini, Hari Mohan, Govindasamy MugeshAbstract:Horseradish peroxidase (HRP) inhibition and glutathione peroxidase (GPx) activities of ebselen and some related derivatives are described. These studies show that ebselen and ebselen ditelluride $(EbTe_2)$ with significant antioxidant activity, inhibit the HRP-catalyzed oxidation reactions. In addition, inhibition of lipid peroxidation and singlet oxygen quenching studies were carried out. Although the inhibition of HRP by ebselen is comparable with that of $EbTe_2$, the inhibitory effect on c-radiation induced lipid peroxidation and the GPx activity of ebselen is found to be much higher than that of $EbTe_2$.
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glutathione peroxidase gpx like antioxidant activity of the Organoselenium drug ebselen unexpected complications with thiol exchange reactions
Journal of the American Chemical Society, 2005Co-Authors: Bani Kanta Sarma, Govindasamy MugeshAbstract:The factors that are responsible for the relatively low glutathione peroxidase (GPx)-like antioxidant activity of Organoselenium compounds such as ebselen (1, 2-phenyl-1,2-benzisoselenazol-3(2H)-one) in the reduction of hydroperoxides with aromatic thiols such as benzenethiol and 4-methylbenzenethiol as cosubstrates are described. Experimental and theoretical investigations reveal that the relatively poor GPx-like catalytic activity of Organoselenium compounds is due to the undesired thiol exchange reactions that take place at the selenium center in the selenenyl sulfide intermediate. This study suggests that any substituent that is capable of enhancing the nucleophilic attack of thiol at sulfur in the selenenyl sulfide state would enhance the antioxidant potency of Organoselenium compounds such as ebselen. It is proved that the use of thiol having an intramolecularly coordinating group would enhance the biological activity of ebselen and other Organoselenium compounds. The presence of strong S···N or S···O interactions in the selenenyl sulfide state can modulate the attack of an incoming nucleophile (thiol) at the sulfur atom of the -Se-S- bridge and enhance the GPx activity by reducing the barrier for the formation of the active species selenol.
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Synthetic Organoselenium compounds as antioxidants:glutathione peroxidase activity
Chemical Society Reviews, 2000Co-Authors: Govindasamy Mugesh, Harkesh B. SinghAbstract:Organoselenium compounds find applications in organic synthesis, materials synthesis, ligand chemistry and biologically relevant processes. This review deals with the use of various synthetic Organoselenium compounds as mimics of glutathione peroxidase (GPx), a selenoenzyme which catalyses the reduction of a variety of hydroperoxides and protects the cell membranes from oxidative damage. The mechanism by which these compounds catalyse the reduction of peroxides is also reviewed. The cyclic selenenamides and diselenides with suitably positioned substituents exert their catalytic activity by a mechanism similar to that of the natural enzyme.
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INTRAMOLECULAR SE ... N NONBONDING INTERACTIONS IN LOW-VALENT Organoselenium DERIVATIVES : A DETAILED STUDY BY 1H AND 77SE NMR SPECTROSCOPY AND X-RAY CRYSTALLOGRAPHY
Chemistry: A European Journal, 1999Co-Authors: Govindasamy Mugesh, Harkesh B. Singh, Arunashree Panda, Ray J. ButcherAbstract:A series of novel low-valent Organoselenium compounds stabilized by Se···N intramolecular interactions (such as the one in the figure) were synthesized, characterized, and examined for Se···N nonbonding interactions. A correlation between Se···N intramolecular distance and 77 Se chemical shift is attempted.
João Rocha - One of the best experts on this subject based on the ideXlab platform.
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Organoselenium compounds as mimics of selenoproteins and thiol modifier agents
Metallomics, 2017Co-Authors: Nilda Vargas Barbosa, Cristina W. Nogueira, Pablo A. Nogara, Andreza Fabro De, Michael Aschner, João RochaAbstract:Selenium is an essential trace element for animals and its role in the chemistry of life relies on a unique functional group: the selenol (–SeH) group. The selenol group participates in critical redox reactions. The antioxidant enzymes glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) exemplify important selenoproteins. The selenol group shares several chemical properties with the thiol group (–SH), but it is much more reactive than the sulfur analogue. The substitution of S by Se has been exploited in organic synthesis for a long time, but in the last 4 decades the re-discovery of ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) and the demonstration that it has antioxidant and therapeutic properties has renovated interest in the field. The ability of ebselen to mimic the reaction catalyzed by GPx has been viewed as the most important molecular mechanism of action of this class of compound. The term GPx-like or thiol peroxidase-like reaction was previously coined in the field and it is now accepted as the most important chemical attribute of Organoselenium compounds. Here, we will critically review the literature on the capacity of Organoselenium compounds to mimic selenoproteins (particularly GPx) and discuss some of the bottlenecks in the field. Although the GPx-like activity of Organoselenium compounds contributes to their pharmacological effects, the superestimation of the GPx-like activity has to be questioned. The ability of these compounds to oxidize the thiol groups of proteins (the thiol modifier effects of Organoselenium compounds) and to spare selenoproteins from inactivation by soft-electrophiles (MeHg+, Hg2+, Cd2+, etc.) might be more relevant for the explanation of their pharmacological effects than their GPx-like activity. In our view, the exploitation of the thiol modifier properties of Organoselenium compounds can be harnessed more rationally than the use of low mass molecular structures to mimic the activity of high mass macromolecules that have been shaped by millions to billions of years of evolution.
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The combination of Organoselenium compounds and guanosine prevents glutamate-induced oxidative stress in different regions of rat brains.
Brain Research, 2011Co-Authors: Cristiane L. Dalla Corte, João Rocha, Luiza Lena Bastos, Fernando Dobrachinski, Félix Alexandre Antunes SoaresAbstract:Abstract This study was designed to investigate the protective effects of the combination of guanosine and 2 Organoselenium compounds (ebselen and diphenyl diselenide) against glutamate-induced oxidative stress in different regions of rat brains. Glutamate caused an increase in reactive oxygen species (ROS) generation and a decrease in [3H]-glutamate uptake in striatal, cortical, and hippocampal slices. Guanosine, ebselen, and diphenyl diselenide prevented glutamate-induced ROS production in striatal, cortical and hippocampal slices. The combination of guanosine with Organoselenium compounds was more effective against glutamate-induced ROS production than the individual compounds alone. Guanosine prevented [3H]-glutamate uptake inhibition in striatal, cortical, and hippocampal slices. Thus, protection against the harmful effects of glutamate is possibly due to the combination of the antioxidant properties of Organoselenium compounds and the stimulatory effect of guanosine on glutamate uptake. In conclusion, the combination of antioxidants and glutamatergic system modulators could be considered a potential therapy against the prooxidant effects of glutamate.
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Protective effects of Organoselenium compounds against methylmercury-induced oxidative stress in mouse brain mitochondrial-enriched fractions
Brazilian Journal of Medical and Biological Research, 2011Co-Authors: Daiane Francine Meinerz, João Rocha, Antonio L Braga, M.t. De Paula, Bruna Comparsi, M.u. Silva, A.e. Schmitz, H.c. Braga, Paulo S. Taube, Alcir Luiz DafreAbstract:We evaluated the potential neuroprotective effect of 1-100 µM of four Organoselenium compounds: diphenyl diselenide, 3’3-ditrifluoromethyldiphenyl diselenide, p-methoxy-diphenyl diselenide, and p-chloro-diphenyl diselenide, against methylmercury-induced mitochondrial dysfunction and oxidative stress in mitochondrial-enriched fractions from adult Swiss mouse brain. Methylmercury (10-100 µM) significantly decreased mitochondrial activity, assessed by MTT reduction assay, in a dose-dependent manner, which occurred in parallel with increased glutathione oxidation, hydroperoxide formation (xylenol orange assay) and lipid peroxidation end-products (thiobarbituric acid reactive substances, TBARS). The co-incubation with diphenyl diselenide (100 µM) completely prevented the disruption of mitochondrial activity as well as the increase in TBARS levels caused by methylmercury. The compound 3’3-ditrifluoromethyldiphenyl diselenide provided a partial but significant protection against methylmercuryinduced mitochondrial dysfunction (45.4 ± 5.8% inhibition of the methylmercury effect). Diphenyl diselenide showed a higher thiol peroxidase activity compared to the other three compounds. Catalase blocked methylmercury-induced TBARS, pointing to hydrogen peroxide as a vector during methylmercury toxicity in this model. This result also suggests that thiol peroxidase activity of Organoselenium compounds accounts for their protective actions against methylmercury-induced oxidative stress. Our results show that diphenyl diselenide and potentially other Organoselenium compounds may represent important molecules in the search for an improved therapy against the deleterious effects of methylmercury as well as other mercury compounds.
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guanosine and synthetic Organoselenium compounds modulate methylmercury induced oxidative stress in rat brain cortical slices involvement of oxidative stress and glutamatergic system
Toxicology in Vitro, 2009Co-Authors: Daniel Henrique Roos, Marcelo Farina, Cristina W. Nogueira, Nilda Vargas Barbosa, Michael Aschner, Robson Luiz Puntel, Matheus Mulling Dos Santos, Diogo Onofre Gomes De Souza, Marilise Escobar Burger, João RochaAbstract:Abstract Excessive formation of reactive oxygen species (ROS) and disruption of glutamate uptake have been pointed as two key mechanisms in methylmercury-toxicity. Thus, here we investigate the involvement of glutamatergic system in methylmercury (MeHg) neurotoxicity and whether diphenyl diselenide, ebselen and guanosine could protect cortical rat brain slices from MeHg-induced ROS generation. MeHg (100 and 200 μM) increased 2′,7′-dichlorodihydrofluorescin (DCFH) oxidation after 2 h of exposure. At 50 μM, MeHg increased DCFH oxidation only after 5 h of exposure. Guanosine (1 and 5 μM) did not caused any effect per se; however, it blocked the increase in DCFH caused by 200 or 50 μM MeHg. Ebselen (5 and 10 μM) decreased significantly the DCFH oxidation after 2 and 5 h of exposure to MeHg. Diphenyl diselenide (5 μM) did not change the basal DCFH oxidation, but abolished the pro-oxidant effect of MeHg. MK-801 also abolished the pro-oxidant effect of MeHg. These results demonstrate for the first time the potential antioxidant properties of organoseleniun compounds and guanosine against MeHg-induced ROS generation after short-term exposure in a simple in vitro model. In conclusion, endogenous purine (guanosine) and two synthetic Organoselenium compounds can modulate the pro-oxidant effect of MeHg in cortical brain slices.
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diphenyl ditelluride and methylmercury induced hyperphosphorilation of the high molecular weight neurofilament subunit is prevented by Organoselenium compounds in cerebral cortex of young rats
Toxicology, 2006Co-Authors: Claudia Funchal, João Rocha, Gilson Zeni, Maria Beatriz Moretto, Lilian Vivian, Regina PessoapureurAbstract:Abstract Organotellurides are important intermediates in organic synthesis and, consequently, the occupational exposure to them is a constant risk for laboratory workers. These compounds can elicit many neurotoxic events in the central nervous system (CNS) that are associated with several neurological symptoms. In contrast, Organoselenium compounds are considered to exert neuroprotective actions on such effects. Neurofilaments (NF) are important cytoskeletal proteins and phosphorylation/dephosphorylation of NF is important to stabilize the cytoskeleton. In this work we investigated the potential protective ability of the selenium compounds ebselen and diphenyl diselenide (PhSe) 2 against the effect of diphenyl ditelluride (PhTe) 2 and methylmercury (MeHg) on the total (phosphorylated plus nonphosphorylated) and phosphorylated immunocontent of the high molecular weight neurofilament subunit (NF-H) from slices of cerebral cortex of 17-day-old rats. We observed that 1 μM MeHg induced hyperphosphorylation, increasing the total immunocontent of this subunit of the high-salt Triton insoluble NF-H. Otherwise, 15 μM (PhTe) 2 induced hyperphosphorylation of the high-salt Triton insoluble NF-H without altering the total immunocontent of this protein into the cytoskeletal fraction. Concerning the selenium compounds, 15 μM (PhSe) 2 and 5 μM ebselen did not induce alteration per se on the in vitro phosphorylation of NF-H. In addition, (PhSe) 2 and ebselen at these concentrations, presented a protective effect against the action of (PhTe) 2 and MeHg, on the immunoreactivity of NF-H. Considering that hyperphosphorylation of NF-H is associated with neuronal dysfunction it is probable that the effects of (PhTe) 2 and MeHg could be related to the remarkable neurotoxicity of these organocalcogenides. Furthermore the neuroprotective action of selenium compounds against (PhTe) 2 and MeHg effects could be a promising route to be exploited for a possible treatment of calcogenides poisoning.
Anton Amann - One of the best experts on this subject based on the ideXlab platform.
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product ion distributions for the reactions of no with some physiologically significant volatile organosulfur and Organoselenium compounds obtained using a selective reagent ionization time of flight mass spectrometer
Rapid Communications in Mass Spectrometry, 2014Co-Authors: Pawel Mochalski, Karl Unterkofler, Patrik Spaněl, David Smith, Anton AmannAbstract:RATIONALE The reactions of NO+ with volatile organic compounds (VOCs) in Selective Reagent Ionization Time-of-Flight Mass Spectrometry (SRI-TOF-MS) reactors are relatively poorly known, inhibiting their use for trace gas analysis. The rationale for this product ion distribution study was to identify the major product ions of the reactions of NO+ ions with 13 organosulfur compounds and 2 Organoselenium compounds in an SRI-TOF-MS instrument and thus to prepare the way for their analysis in exhaled breath, in skin emanations and in the headspace of urine, blood and cell and bacterial cultures. METHODS Product ion distributions have been investigated by a SRI-TOF-MS instrument at an E/N in the drift tube reactor of 130 Td for both dry air and humid air (4.9% absolute humidity) used as the matrix gas. The investigated species were five monosulfides (dimethyl sulfide, ethyl methyl sulfide, methyl propyl sulfide, allyl methyl sulfide and methyl 5-methyl-2-furyl sulfide), dimethyl disulfide, dimethyl trisulfide, thiophene, 2-methylthiophene, 3-methylthiophene, methanethiol, allyl isothiocyanate, dimethyl sulfoxide, and two selenium compounds – dimethyl selenide and dimethyl diselenide. RESULTS Charge transfer was seen to be the dominant reaction mechanism in all reactions under study forming the M+ cations. For methanethiol and allyl isothiocyanate significant fractions were also observed of the stable adduct ions NO+M, formed by ion-molecule association, and [M–H]+ ions, formed by hydride ion transfer. Several other minor product channels are seen for most reactions indicating that the nascent excited intermediate (NOM)+* adduct ions partially fragment along other channels, most commonly by the elimination of neutral CH3, CH4 and/or C2H4 species that are probably bound to an NO molecule. Humidity had little effect on the product ion distributions. CONCLUSIONS The findings of this study are of particular importance for data interpretation in studies of volatile organosulfur and volatile Organoselenium compounds employing SRI-TOF-MS in the NO+ mode. © 2014 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.
Cristina W. Nogueira - One of the best experts on this subject based on the ideXlab platform.
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Toxicology and pharmacology of synthetic Organoselenium compounds: an update
Archives of Toxicology, 2021Co-Authors: Cristina W. Nogueira, Nilda V. Barbosa, João B. T. RochaAbstract:Here, we addressed the pharmacology and toxicology of synthetic Organoselenium compounds and some naturally occurring Organoselenium amino acids. The use of selenium as a tool in organic synthesis and as a pharmacological agent goes back to the middle of the nineteenth and the beginning of the twentieth centuries. The rediscovery of ebselen and its investigation in clinical trials have motivated the search for new Organoselenium molecules with pharmacological properties. Although ebselen and diselenides have some overlapping pharmacological properties, their molecular targets are not identical. However, they have similar anti-inflammatory and antioxidant activities, possibly, via activation of transcription factors, regulating the expression of antioxidant genes. In short, our knowledge about the pharmacological properties of simple Organoselenium compounds is still elusive. However, contrary to our early expectations that they could imitate selenoproteins, Organoselenium compounds seem to have non-specific modulatory activation of antioxidant pathways and specific inhibitory effects in some thiol-containing proteins. The thiol-oxidizing properties of Organoselenium compounds are considered the molecular basis of their chronic toxicity; however, the acute use of Organoselenium compounds as inhibitors of specific thiol-containing enzymes can be of therapeutic significance. In summary, the outcomes of the clinical trials of ebselen as a mimetic of lithium or as an inhibitor of SARS-CoV-2 proteases will be important to the field of Organoselenium synthesis. The development of computational techniques that could predict rational modifications in the structure of Organoselenium compounds to increase their specificity is required to construct a library of thiol-modifying agents with selectivity toward specific target proteins.
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Organoselenium compounds as mimics of selenoproteins and thiol modifier agents
Metallomics, 2017Co-Authors: Nilda Vargas Barbosa, Cristina W. Nogueira, Pablo A. Nogara, Andreza Fabro De, Michael Aschner, João RochaAbstract:Selenium is an essential trace element for animals and its role in the chemistry of life relies on a unique functional group: the selenol (–SeH) group. The selenol group participates in critical redox reactions. The antioxidant enzymes glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) exemplify important selenoproteins. The selenol group shares several chemical properties with the thiol group (–SH), but it is much more reactive than the sulfur analogue. The substitution of S by Se has been exploited in organic synthesis for a long time, but in the last 4 decades the re-discovery of ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) and the demonstration that it has antioxidant and therapeutic properties has renovated interest in the field. The ability of ebselen to mimic the reaction catalyzed by GPx has been viewed as the most important molecular mechanism of action of this class of compound. The term GPx-like or thiol peroxidase-like reaction was previously coined in the field and it is now accepted as the most important chemical attribute of Organoselenium compounds. Here, we will critically review the literature on the capacity of Organoselenium compounds to mimic selenoproteins (particularly GPx) and discuss some of the bottlenecks in the field. Although the GPx-like activity of Organoselenium compounds contributes to their pharmacological effects, the superestimation of the GPx-like activity has to be questioned. The ability of these compounds to oxidize the thiol groups of proteins (the thiol modifier effects of Organoselenium compounds) and to spare selenoproteins from inactivation by soft-electrophiles (MeHg+, Hg2+, Cd2+, etc.) might be more relevant for the explanation of their pharmacological effects than their GPx-like activity. In our view, the exploitation of the thiol modifier properties of Organoselenium compounds can be harnessed more rationally than the use of low mass molecular structures to mimic the activity of high mass macromolecules that have been shaped by millions to billions of years of evolution.
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Toxicology and pharmacology of selenium: emphasis on synthetic Organoselenium compounds
Archives of Toxicology, 2011Co-Authors: Cristina W. Nogueira, João B. T. RochaAbstract:The advance in the area of synthesis and reactivity of Organoselenium, as well as the discovery that selenium was the cause of severe intoxication episodes of livestock in the 1930s and the subsequent determination that selenium was an essential trace element in the diet for mammals, has motivated intense studies of the biological properties of both organic and inorganic selenium compounds. In this review, we shall cover a wide range of toxicological and pharmacological effects, in which Organoselenium compounds are involved but the effects of inorganic compounds were not discussed in detail here. The molecular toxicity of inorganic selenium was described in relation to its interaction with endogenous –SH groups to allow a comparison with that of synthetic Organoselenium compounds. Furthermore, in view of the recent points of epidemiological evidence that overexposure to selenium can facilitate the appearance of chronic degenerative diseases, we also briefly revised the history of selenium toxicity and physiology and how environmental selenium can reach inside the mammalian cells. The biological narrative of the element selenium, in the last century, has been marked by a contrast between its toxic and its beneficial effects. Thus, the potential therapeutic use of simple Organoselenium compounds has not yet been sufficiently explored and, consequently, we cannot discard this class of compounds as promising pharmaceutical agents. In effect, the future of the organochalcogens as pharmacological agents will depend on more detailed toxicological studies in the oncoming years.
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guanosine and synthetic Organoselenium compounds modulate methylmercury induced oxidative stress in rat brain cortical slices involvement of oxidative stress and glutamatergic system
Toxicology in Vitro, 2009Co-Authors: Daniel Henrique Roos, Marcelo Farina, Cristina W. Nogueira, Nilda Vargas Barbosa, Michael Aschner, Robson Luiz Puntel, Matheus Mulling Dos Santos, Diogo Onofre Gomes De Souza, Marilise Escobar Burger, João RochaAbstract:Abstract Excessive formation of reactive oxygen species (ROS) and disruption of glutamate uptake have been pointed as two key mechanisms in methylmercury-toxicity. Thus, here we investigate the involvement of glutamatergic system in methylmercury (MeHg) neurotoxicity and whether diphenyl diselenide, ebselen and guanosine could protect cortical rat brain slices from MeHg-induced ROS generation. MeHg (100 and 200 μM) increased 2′,7′-dichlorodihydrofluorescin (DCFH) oxidation after 2 h of exposure. At 50 μM, MeHg increased DCFH oxidation only after 5 h of exposure. Guanosine (1 and 5 μM) did not caused any effect per se; however, it blocked the increase in DCFH caused by 200 or 50 μM MeHg. Ebselen (5 and 10 μM) decreased significantly the DCFH oxidation after 2 and 5 h of exposure to MeHg. Diphenyl diselenide (5 μM) did not change the basal DCFH oxidation, but abolished the pro-oxidant effect of MeHg. MK-801 also abolished the pro-oxidant effect of MeHg. These results demonstrate for the first time the potential antioxidant properties of organoseleniun compounds and guanosine against MeHg-induced ROS generation after short-term exposure in a simple in vitro model. In conclusion, endogenous purine (guanosine) and two synthetic Organoselenium compounds can modulate the pro-oxidant effect of MeHg in cortical brain slices.
João B. T. Rocha - One of the best experts on this subject based on the ideXlab platform.
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Toxicology and pharmacology of synthetic Organoselenium compounds: an update
Archives of Toxicology, 2021Co-Authors: Cristina W. Nogueira, Nilda V. Barbosa, João B. T. RochaAbstract:Here, we addressed the pharmacology and toxicology of synthetic Organoselenium compounds and some naturally occurring Organoselenium amino acids. The use of selenium as a tool in organic synthesis and as a pharmacological agent goes back to the middle of the nineteenth and the beginning of the twentieth centuries. The rediscovery of ebselen and its investigation in clinical trials have motivated the search for new Organoselenium molecules with pharmacological properties. Although ebselen and diselenides have some overlapping pharmacological properties, their molecular targets are not identical. However, they have similar anti-inflammatory and antioxidant activities, possibly, via activation of transcription factors, regulating the expression of antioxidant genes. In short, our knowledge about the pharmacological properties of simple Organoselenium compounds is still elusive. However, contrary to our early expectations that they could imitate selenoproteins, Organoselenium compounds seem to have non-specific modulatory activation of antioxidant pathways and specific inhibitory effects in some thiol-containing proteins. The thiol-oxidizing properties of Organoselenium compounds are considered the molecular basis of their chronic toxicity; however, the acute use of Organoselenium compounds as inhibitors of specific thiol-containing enzymes can be of therapeutic significance. In summary, the outcomes of the clinical trials of ebselen as a mimetic of lithium or as an inhibitor of SARS-CoV-2 proteases will be important to the field of Organoselenium synthesis. The development of computational techniques that could predict rational modifications in the structure of Organoselenium compounds to increase their specificity is required to construct a library of thiol-modifying agents with selectivity toward specific target proteins.
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Toxicology and pharmacology of selenium: emphasis on synthetic Organoselenium compounds
Archives of Toxicology, 2011Co-Authors: Cristina W. Nogueira, João B. T. RochaAbstract:The advance in the area of synthesis and reactivity of Organoselenium, as well as the discovery that selenium was the cause of severe intoxication episodes of livestock in the 1930s and the subsequent determination that selenium was an essential trace element in the diet for mammals, has motivated intense studies of the biological properties of both organic and inorganic selenium compounds. In this review, we shall cover a wide range of toxicological and pharmacological effects, in which Organoselenium compounds are involved but the effects of inorganic compounds were not discussed in detail here. The molecular toxicity of inorganic selenium was described in relation to its interaction with endogenous –SH groups to allow a comparison with that of synthetic Organoselenium compounds. Furthermore, in view of the recent points of epidemiological evidence that overexposure to selenium can facilitate the appearance of chronic degenerative diseases, we also briefly revised the history of selenium toxicity and physiology and how environmental selenium can reach inside the mammalian cells. The biological narrative of the element selenium, in the last century, has been marked by a contrast between its toxic and its beneficial effects. Thus, the potential therapeutic use of simple Organoselenium compounds has not yet been sufficiently explored and, consequently, we cannot discard this class of compounds as promising pharmaceutical agents. In effect, the future of the organochalcogens as pharmacological agents will depend on more detailed toxicological studies in the oncoming years.