RESUMEN
There remains today a critical need for new antiviral agents, particularly in view of the alarming increase in drug resistance and associated issues. The marine environment has been a prolific contributor towards the identification of novel therapeutic agents in the recent few decades. Added to this, glycans (or carbohydrate- or sugar-based compounds) have in very recent decades made outstanding contributions to the development of novel therapeutics. This review brings together these significant facets of modern drug discovery by presenting the reported literature on glycans derived from marine organisms that possess antiviral activity.The glycans have been grouped together based on the marine organism they were isolated from, namely, (1) bacteria, (2) chromists, (3) plants and (4) animals. For chromists, glycans are further subsectioned into Ochrophyta (brown algae), Miozoa (according to www.algaebase.org ; also called Myzozoa according to WoRMS, www.marinespecies.org ) (dinoflagellates) and Bacillariophyta (diatoms). For plants, glycans are further subsectioned into Chlorophyta, Rhodophyta and Tracheophyta. Glycans isolated to date are reported as alginates, chitosan, extracellular polysaccharides, fucans (e.g. fucoidans), galactans (e.g. carrageenans), glycolipids, glycosaminoglycans, glycosides, glycosylated haemocyanin, laminarans, mannans, polysaccharides (not defined), rhamnans and xylomannans. Interestingly, many of the glycans displaying antiviral properties are sulfated.Reports indicate that marine-sourced glycans have exhibited antiviral activity against African swine fever virus, cytomegalovirus, dengue virus, Epstein-Barr virus, encephalomyocarditis virus, human immunodeficiency virus, hepatitis C virus, herpes simplex virus, human cytomegalovirus, human papilloma virus, human rhino virus, influenza virus, Japanese encephalitis virus, murine leukaemia virus, murine sarcoma virus, Newcastle disease virus, parainfluenza virus, respiratory syncytial virus, Semliki Forest virus, tobacco mosaic virus, vaccinia virus, varicella zoster virus, viral haemorrhagic septicaemia virus and vesicular stomatitis virus. Selected representative glycan structures are presented in Fig. 20.1.
Asunto(s)
Antivirales/metabolismo , Organismos Acuáticos/metabolismo , Polisacáridos/metabolismo , Animales , Antivirales/química , Antivirales/aislamiento & purificación , Humanos , Polisacáridos/química , Polisacáridos/aislamiento & purificaciónRESUMEN
The glycosyltransferase enzymes (Lgts) responsible for the biosynthesis of the lipooligosaccharide-derived oligosaccharide structures from Moraxella catarrhalis have been investigated. This upper respiratory tract pathogen is responsible for a spectrum of illnesses, including otitis media (middle ear infection) in children, and contributes to exacerbations of chronic obstructive pulmonary disease in elderly patients. To investigate the function of the glycosyltransferase enzymes involved in the biosynthesis of lipooligosaccharide of M. catarrhalis and to gain some insight into the mechanism of serotype specificity for this microorganism, mutant strains of M. catarrhalis were produced. Examination by NMR and MS of the oligosaccharide structures produced by double-mutant strains (2951lgt1/4Delta and 2951lgt5/4Delta) and a single-mutant strain (2951lgt2Delta) of the bacterium has allowed us to propose a model for the serotype-specific expression of lipooligosaccharide in M. catarrhalis. According to this model, the presence/absence of Lgt4 and the Lgt2 allele determines the lipooligosaccharide structure produced by a strain. Furthermore, it is concluded that Lgt4 functions as an N-acetylglucosylamine transferase responsible for the addition of an alpha-D-GlcNAc (1-->2) glycosidic linkage to the (1-->4) branch, and also that there is competition between the glycosyltransferases Lgt1 and Lgt4. That is, in the presence of an active Lgt4, GlcNAc is preferentially added to the (1-->4) chain of the growing oligosaccharide, instead of Glc. In serotype B strains, which lack Lgt4, Lgt1 adds a Glc at this position. This implies that active Lgt4 has a much higher affinity/specificity for the beta-(1-->4)-linked Glc on the (1-->4) branch than does Lgt1.
Asunto(s)
Glicosiltransferasas/fisiología , Lipopolisacáridos/biosíntesis , Moraxella catarrhalis/metabolismo , Glicosiltransferasas/genética , Lipopolisacáridos/química , Espectroscopía de Resonancia Magnética , Moraxella catarrhalis/clasificación , Serotipificación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
The leaves of Eremophila gilesii have been used traditionally to treat colds, headaches, sores, and chest pains. Our previous screening of Australian native plants showed that the methanol extract of the aerial parts of E. gilesii demonstrated notable inhibition of ADP-induced human platelet aggregation and serotonin release. Subsequent fractionation on the methanol extract led to the isolation of two phenylethanoid glycosides, verbascoside (1) and poliumoside (2). This is the first study reporting the presence of phenylethanoid glycosides in E. gilesii.
Asunto(s)
Glucósidos/aislamiento & purificación , Glicósidos/aislamiento & purificación , Fenoles/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Australia , Glucósidos/farmacocinética , Glicósidos/farmacología , Humanos , Fenoles/farmacocinética , Extractos Vegetales/farmacología , Agregación Plaquetaria/efectos de los fármacosRESUMEN
Extracts of Australian plants were screened to detect constituents affecting adenosine di-phosphate (ADP) induced platelet aggregation and [14C]5-hydroxytryptamine (5-HT) release. Extracts of four tested plants including, Eremophila gilesii, Erythrina vespertilio, Cymbopogon ambiguus, and Santalum acuminatum, were found to cause significant inhibition of platelet 5-HT release. Inhibition levels ranged from 56-98%, and was not due to the non-specific effects of protein binding tannins. These extracts, and those we have previously identified as being active, were examined further to determine if they affect epinephrine (EPN), arachidonic acid (A.A) or collagen stimulated platelet aggregation and 5-HT release. Among those extracts investigated, we found that both the methanolic extract of E. vespertilio and the dichloromethane (DCM) extract of C. ambiguus were most potent and caused significant inhibition of platelet activation induced by EPN, A.A and to a lesser extent by collagen. Inhibition of ADP induced platelet 5-HT release by both of these extracts, was dose-dependent, with IC50 values for E. vespertilio and C. ambiguus estimated to be 20.4 microl (1.855 mg/ml) and 8.34 microl (0.758 mg/ml), respectively. Overall, C. ambiguus exhibited most activity and also caused dose-dependent inhibition of A.A induced platelet activation. These results indicate that inhibition may occur specifically at a site within the A.A pathway, and suggest the presence of a cyclo-oxygenase inhibitor. Both E. vespertilio and C. ambiguus are reported to be traditional headache treatments, with the present study providing evidence that they affect 5-HT release.
Asunto(s)
Plaquetas/efectos de los fármacos , Erythrina , Trastornos Migrañosos/tratamiento farmacológico , Extractos Vegetales/farmacología , Plantas Medicinales , Serotonina/biosíntesis , Adenosina Difosfato/farmacología , Adulto , Ácido Araquidónico/farmacología , Plaquetas/metabolismo , Colágeno/farmacología , Relación Dosis-Respuesta a Droga , Epinefrina/farmacología , Humanos , Cinética , Metanol/química , Cloruro de Metileno/química , Agregación Plaquetaria/efectos de los fármacosRESUMEN
To identify potential migraine therapeutics, extracts of eighteen plants were screened to detect plant constituents affecting ADP induced platelet aggregation and [14C]5-hydroxytryptamine (5-HT) release. Extracts of the seven plants exhibiting significant inhibition of platelet function were reanalysed in the presence of polyvinyl pyrrolidone (PVP) to remove polyphenolic tannins that precipitate proteins. Two of these extracts no longer exhibited inhibition of platelet activity after removal of tannins. However, extracts of Crataegus monogyna, Ipomoea pes-caprae, Eremophila freelingii, Eremophila longifolia, and Asteromyrtus symphyocarpa still potently inhibited ADP induced human platelet [14C]5-HT release in vitro, with levels ranging from 62 to 95% inhibition. I. pes-caprae, and C. monogyna also caused significant inhibition of ADP induced platelet aggregation. All of these plants have been previously used as traditional headache treatments, except for C. monogyna which is used primarily for protective effects on the cardiovascular system. Further studies elucidating the compounds that are responsible for these anti-platelet effects are needed to determine their exact mechanism of action.
Asunto(s)
Plaquetas/metabolismo , Cefalea/tratamiento farmacológico , Plantas Medicinales , Inhibidores de Agregación Plaquetaria/farmacología , Serotonina/metabolismo , Adenosina Difosfato/farmacología , Adulto , Australia , Plaquetas/efectos de los fármacos , Radioisótopos de Carbono , Relación Dosis-Respuesta a Droga , Humanos , Trastornos Migrañosos/tratamiento farmacológico , Extractos Vegetales/farmacología , Plantas Medicinales/química , Agregación Plaquetaria/efectos de los fármacosRESUMEN
When nitric oxide (NO), generated from nitric acid and copper, was reacted with a series of 9,10-substituted anthracenes, only 9,10-dimethylanthracene gave EPR detectable nitroxide radicals, although the expected bicyclic nitroxide arising from cheletropic NO addition across the 9,10-positions was not observed. Purity of the NO is crucial as the presence of higher oxides of nitrogen leads to radicals by hydrogen abstraction which are trapped by NO and the resultant nitroso compounds produce stable nitroxides detectable by EPR. In contrast the acyclic system, 3,4-diphenyl-2,5-dimethyl-2,4-hexadiene gives rise to an EPR spectrum consistent with cheletropic NO addition, although higher oxides of nitrogen again mediate the formation of different nitroxides.