Synthetic interferon inducers

Clercq, Erik De

doi:10.1007/3-540-06873-2_17

Cited by 31 publications

(6 citation statements)

References 171 publications

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“…Conceivably, signal amplification could result from activation by viral dsRNA of the IFN-inducible, dsRNA-dependent protein kinase (PKIFN~sRNA), and its ensuing phosphorylating capacity (Lasky et al, 1982;Hovanessian et al, 1986). Furthermore, IFN induction and activation of PKIFN~tsP, NA display similar structural requirements: both reactions require an uninterrupted run of 6 to 12 base pairs and a minimal length of about 50 base pairs (DeClercq, 1974;Greene et al, 1978;Minks et al, 1979).…”

mentioning

confidence: 99%

Interferon Induction by Viruses. XVI. 2-Aminopurine Blocks Selectively and Reversibly an Early Stage in Interferon Induction

Marcus

Sekellick

1988

Journal of General Virology

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SUMMARYA purine analogue, 2-aminopurine, reported to act as an inhibitor of protein kinase, selectively, reversibly and in a dose-dependent manner blocked a very early stage in interferon induction. With chick embryo cells and mouse L cells as hosts, and different viral inducers of interferon, maximal effects of 2-aminopurine were observed during the first 4 h of induction. At 10 mM-2-aminopurine there was a 20-fold reduction in the yield of interferon from both cell types. 2-Aminopurine and actinomycin D both prevented interferon induction with the same time course, indicating a transcriptional block to induction; however, only the action of the former was reversed upon removal of the drug. Addition of 2-aminopurine to an agarose overlay resulted in high efficiency plaque formation by vesicular stomatitis virus New Jersey (Hazelhurst) under conditions where endogenous induction of interferon and its feedback action on aged chick embryo cells normally prevented plaque formation. Two other inducible systems, representing genes involved in interferon action (both its development and activation), and those of heat shock, were not affected by 2-aminopurine. A model is presented implicating the interferon-inducible dsRNA-dependent protein kinase as an interferon induction receptor which, on interaction with dsRNA, generates an amplified signal via phosphorylation that ultimately derepresses the interferon gene(s).

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mentioning

confidence: 99%

Interferon Induction by Viruses. XVI. 2-Aminopurine Blocks Selectively and Reversibly an Early Stage in Interferon Induction

Marcus

Sekellick

1988

Journal of General Virology

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“…This finding was patented and licensed by Stanford University to the company Wyeth, who abandoned the further pursuit of poly(As-Us) a few years later. Back in Leuven, I continued the study of the mechanism of interferon induction by poly(I)·poly(C), and the structural requirements of dsRNAs to induce interferon, and with Bill Carter, I reviewed the role of dsRNA during the virus infection process …”

Section: Interferon Inducersmentioning

confidence: 99%

Fifty Years in Search of Selective Antiviral Drugs

Clercq

2019

J. Med. Chem.

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Fifty years of research (1968Fifty years of research ( −2018 toward the identification of selective antiviral drugs have been primarily focused on antiviral compounds active against DNA viruses (HSV, VZV, CMV, HBV) and retroviruses (HIV). For the treatment of HSV infections the aminoacyl esters of acyclovir were designed, and valacyclovir became the successor of acyclovir in the treatment of HSV and VZV infections. BVDU (brivudin) still stands out as the most potent among the marketed compounds for the treatment of VZV infections (i.e., herpes zoster). In the treatment of HIV infections 10 tenofovir-based drug combinations have been marketed, and tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) have also proved effective in the treatment of HBV infections. As a spin-off of our anti-HIV research, a CXCR4 antagonist AMD-3100 was found to be therapeutically useful as a stem cell mobilizer, and has since 10 years been approved for the treatment of some hematological malignancies.

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“…Одним з найефективніших противірусних за-собів широкого спектра дії є аміксин (1), якому притаманні: здатність індукувати інтерферон [1][2][3][4][5], імунотропна активність [6][7][8], інгібування репро-дукції вірусів в інтерфероннезалежний спосіб [9], протизапальна [10][11][12] та антиканцерогенна [13] дія, протипухлинна [14,15] та радіопротекторна активність [16][17][18], афінітет до a7нАХР [19], ан-тигіпоксична активність [20], здатність інгібува-ти перекисне окиснення ліпідів [21]. Якщо щодо деяких видів активності аміксину механізм їхньої реалізації можна вважати встановленим більш-менш точно, то стосовно механізму реалізації про-тивірусної та інтерфероніндукуючої активності досі немає загальноприйнятої точки зору.…”

Section: Issn 2308-8303 в смеси ксилола с водным раствором йодида натunclassified

Synthesis and cytotoxicity of aminoethoxydiphenyls

Zanoza¹,

Maltzev²,

Lyakhov³

et al. 2014

J. org. pharm. chem.

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В ІЧ-спектрах наявні смуги поглинання, характерні для зв'язків C-H (аром.), C-H (аліф), C-O-C та NH протонованих термінальних аміногруп. У спектрах 1 H-ЯМР наявні сигнали від ароматич-них та аліфатичних протонів, мультиплетність та інтегральна інтенсивність яких відповідає припи-суваним структурам. На клітинах ПТП вивчена цитотоксичність низки 4,4'-біс-(2-аміноетокси)дифе-нілів, значення якої зіставні з токсичністю аміксину та знаходяться в діапазоні від низьких до помірних. SYNTHESIS AND CYTOTOXICITY OF AMINOETHOXYDIPHENYLS to induce IFI in biphenyl derivatives that are incapable to intercalate in NA indicates the possibility of implementing alternative mechanisms. This determined our interest to the study of aminoethoxydiphenyls (AED), which synthesis and investigation of cytotoxicity become the subject of this article. 4,4'-Bis-(2-chloroethoxy)diphenyl was obtained by alkylation of dihydroxydiphenyl with dichloroethane in its mixture with aqueous sodium hydroxide (20%) in the presence of tetrabutylammonium chloride (TBAC). Series of AED were synthesized by substitution of chlorine by iodine in the mixture of xylene with the aqueous solution of sodium iodide in the presence of TBAC with subsequent amination with primary and secondary amines. The protonated molecular ions (MI) intensive peaks of the compounds synthesized are observed in the mass spectra with FAB ionization. The most common way of MI fragmentation is

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Synthetic interferon inducers

Cited by 31 publications

References 171 publications

Interferon Induction by Viruses. XVI. 2-Aminopurine Blocks Selectively and Reversibly an Early Stage in Interferon Induction

Interferon Induction by Viruses. XVI. 2-Aminopurine Blocks Selectively and Reversibly an Early Stage in Interferon Induction

Fifty Years in Search of Selective Antiviral Drugs

Synthesis and cytotoxicity of aminoethoxydiphenyls

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