Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure–activity requirements

Isaković, Aleksandra; Janković, Teodora; Harhaji, Ljubica; Kostić‐Rajačić, Sladjana; Nikolić, Zoran; Vajs, Vlatka; Trajkovič, Vladimir

doi:10.1016/j.bmc.2008.03.069

Cited by 29 publications

(18 citation statements)

References 37 publications

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“…To evaluate the role of mitochondria in AHSV-induced apoptosis, the mitochondrial membrane potential of AHSV-infected BHK-21 cells was subsequently assessed using with depolarized mitochondrial membranes (Dispersyn et al, 1999). The results are presented as a green/red fluorescence ratio (geomean FL1/FL2), the increase of which indicates mitochondrial membrane depolarization (Isakovic et al, 2008). Flow cytometric analysis of AHSV-infected BHK-21 cells indicated a progressive loss of mitochondrial membrane potential from 0 to 24 h post-infection, as evidenced by an increase in the green-to-red (FL1/FL2) fluorescence form of the mitochondria-binding dye DePsipher ™ (Fig.…”

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confidence: 99%

African horse sickness virus induces apoptosis in cultured mammalian cells

2012

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Infection of mammalian cell cultures with African horse sickness virus (AHSV) is known to result in dramatic cytopathic effects (CPE), but no CPE is observed in infected insect cell cultures despite productive virus replication. The basis for this phenomenon has not yet been investigated, but is suggestive of apoptosis being induced following virus infection of the mammalian cells. To investigate whether AHSV can induce apoptosis in infected mammalian cells, Culicoides variipennis (KC) insect cells and BHK-21 mammalian cells were infected with AHSV-9 and analyzed for morphological and biochemical hallmarks of apoptosis. In contrast to KC cells, infection of BHK-21 cells with AHSV-9 resulted in ultrastructural changes and nuclear DNA fragmentation, both of which are associated with the induction of apoptosis. Results also indicated that AHSV-9 infection of BHK-21 cells resulted in activation of caspase-3, a key agent in apoptosis, and in mitochondrial membrane depolarization. Cumulatively, the data indicate that the intrinsic pathway is activated in AHSVinduced apoptosis.Keywords: African horse sickness virus; Apoptosis; BHK-21 cells; Culicoides variipennis cells; Caspases; Intrinsic pathwayAfrican horse sickness virus (AHSV) is a species in the genus Orbivirus, family Reoviridae (Calisher and Mertens, 1998), and is the causative agent of African horse sickness (AHS), a highly infectious arthropod-borne (Culicoides spp.) disease of equids, of which the mortality rate in horses may exceed 90% (Coetzer and Erasmus, 1994;Guthrie, 2007). Although African horse sickness virus (AHSV) causes severe oedema and haemorrhages in horses, it is asymptomatic in the insect host (Mellor and Hamblin, 2004;Wilson et al., 2009). This is also reflected in tissue culture where AHSV causes rapid cell death in infected mammalian cells in culture, whereas infection of insect cells are unapparent and show no CPE (Mirchamsy et al., 1970;Osawa and Hazrati, 1965). The basis for this differential host response is not known, but may be due to the induction of apoptosis in infected mammalian cells. Indeed, analyses of endothelial cells of animals infected with AHSV indicated ultrastructural changes that could be suggestive of apoptosis (Gómez-Villamandos et al., 1999).Apoptosis is a selective process of physiological cell deletion in response to numerous developmental and environmental stimuli (Kerr et al., 1972). There are two common pathways for the induction of apoptosis, i.e. the extrinsic pathway, which is primarily initiated by virus attachment to receptors, and the intrinsic pathway, which is mediated by damage to the mitochondria (Duprez et al., 2009). Various reports have indicated that infection of mammalian cells by viruses induces apoptosis (Roulston et al., 1999) and in some virus-induced diseases, apoptosis is a pathogenic mechanism that contributes in vivo to cell death, tissue injury and disease severity Samuel et al., 2007). Indeed, the induction of apoptosis has recently been implicated in the pathogenesis of bluetong...

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African horse sickness virus induces apoptosis in cultured mammalian cells

2012

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“…The green DePsipher monomer was detected using the fluorescein channel (FITC-A; FL1) and the red DePsipher aggregates were detected using the propidium iodide channel (PE-A; FL2). The results are presented as a green/red fluorescence ratio (geomean FL1/FL2), the increase of which indicates mitochondrial membrane depolarization (Markovic et al, 2007;Isakovic et al, 2008).…”

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confidence: 99%

Virus uncoating is required for apoptosis induction in cultured mammalian cells infected with African horse sickness virus

Vermaak

Theron

2015

Journal of General Virology

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Infection of cultured mammalian cells with African horse sickness virus (AHSV) is known to induce cell death. To date, the trigger(s) of this response, the apoptotic pathways activated during AHSV infection and the functional consequences of apoptosis on the virus replication cycle have yet to be characterized. This study demonstrated that extracellular treatment of BHK-21 cells with both of the AHSV4 outer capsid proteins, VP2 and VP5, was sufficient to trigger apoptosis. Whether steps in AHSV4 replication subsequent to viral attachment were required for AHSV4-induced apoptosis was also investigated. Apoptosis was induced in BHK-21 cells infected with UV-inactivated AHSV4 and in ribavirin-treated cells infected with AHSV4. However, both AHSV4-and VP2/VP5-stimulated apoptotic responses were inhibited in the presence of the endosomal acidification inhibitors ammonium chloride and chloroquine. These results indicated that uncoating of AHSV4 virions, but not viral transcription or subsequent steps in viral replication, was required for AHSV4 to induce apoptosis in BHK-21 cells. Furthermore, this study showed that both the extrinsic (caspase-8) and intrinsic (caspase-9) apoptotic pathways were induced following AHSV4 infection. The inhibition of caspase activity in AHSV4-infected cells did not diminish AHSV4 replication, but reduced the release and dissemination of progeny viral particles. Taken together, the data indicated that uncoating of AHSV virions was required for apoptosis induction, and that apoptosis enhanced virus spread and release.

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“…for C 25 H 21 FO 2 : C, 80.62; H, 5.68. Found: C, 80.45; H,9,10, White solid, mp 182-184 o C; IR (KBr) ν max /cm -1 …”

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“…The spectral and analytical data for the new compounds were given below. 9,10, White 0, 29.5, 32.1, 34.1, 41.5, 51.0, 114.0, 115.0, 115.2, 117.2, 117.5, 123.7, 125.0, 127.2, 128.5, 129.2, 130.0, 131.4, 131.5, 140.6, 147.8, 164.0, 197.0; Anal. Calc.…”

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Synthesis 12-Aryl or 12-Alkyl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one derivatives catalyzed by dodecatungstophosphoric acid

Wang¹,

Ren²,

Zhang³

et al. 2009

J. Braz. Chem. Soc.

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Um protocolo eficiente para a síntese de derivados de 12-aril ou 12-alquil-8,9,10,12-tetrahidrobenzo[a]xanten-11-one foi desenvolvido via reação de três componentes de aldeído, 2-naftol e 1,3-ciclohexadiona ou 5,5-dimetil-1,3-ciclohexadiona na presença de ácido 12-tungstofosfórico (H 3 PW 12 O 40 ) sem o uso de solvente. A presente metodologia oferece muitas vantagens como altos rendimentos, procedimento simples, baixo custo, curto tempo de reação e condições brandas.An efficient protocol for the synthesis of 12-aryl or 12-alkyl-8,9,10,12-tetrahydro-benzo [a] xanthen-11-one derivatives has been developed via three-component reaction of aldehyde, 2-naphthol and 1,3-cyclohexadione or 5,5-dimethyl-1,3-cyclohexadione in the presence of 12-tungstophosphoric acid (H 3 PW 12 O 40 ) under solvent-free conditions. The present methodology offers several advantages such as high yields, simple procedure, low cost, short reaction times, and mild conditions. Keywords: xanthene, multi-component reaction, 2-naphthol, aldehydes, 12-tungstophosphoric acid, heteropoly acid, solvent-free conditions IntroductionXanthenes and their derivatives have been received special attention due to their diverse array of biological activities such as anti-inflammatory, antibacterial and antiviral activities. [1][2][3] In addition to this, they can be employed as dyes, 4 intracellular pH indicators, 5 molecular probes in chemical biology, 6 and fluorescent materials for visualization of biomolecules. 7 In particular, the xanthone moiety is a core structure of a series of natural products with interesting biological and pharmacological activities. [8][9][10][11][12] Tetrahydroxanthenones are among the most important classes in the family of xanthones due to their distinctive structure and great potential for further transformations. 13,14 Consequently, the development of novel methods for the synthesis of these heterocyclic compounds has been received considerable interest in both organic and medicinal fields. [15][16][17][18] The three-component reaction of aryl aldehydes, 2-naphthol and cyclic 1,3-dicarbonyl compounds has appeared as a novel alternative method for preparation of tetrahydroxanthenones. 19 In this regard, NaHSO 4 • SiO 2 was utilized to catalyze this reaction to afford 12-aryl or 12-alkyl-8,9,10,12-tetrahydro-benzo[a]xanthen-11-one derivatives. However, this method needs to be further improved because some disadvantages such as relatively long reaction times and the use of harmful volatile organic solvent. Therefore, the development of efficient, mild and environmentally benign practical synthetic methods for accessing this type of heterocyclic compounds still remains a great need.In recent years, the application of solid acids in organic synthesis is becoming an area of growing interest. Heteropoly acids (HPAs) are strong solid acids, harmless to the environment and highly stable toward humidity and have flexibility in modifying the acid strength. 21 On the other hand, multi-component reactions (MCRs) offer significant advanta...

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Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure–activity requirements

Cited by 29 publications

References 37 publications

African horse sickness virus induces apoptosis in cultured mammalian cells

African horse sickness virus induces apoptosis in cultured mammalian cells

Virus uncoating is required for apoptosis induction in cultured mammalian cells infected with African horse sickness virus

Synthesis 12-Aryl or 12-Alkyl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one derivatives catalyzed by dodecatungstophosphoric acid

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