Synthesis, cytotoxicity, antiviral activity and interferon inducing ability of 6-(2-aminoethyl)-6H-indolo[2,3-b]quinoxalines

Shibinskaya, Marina O.; Lyakhov, S. A.; Мазепа, А. В.; Андронати, С. А.; Туров, А. В.; Nm, Zholobak; Spivak, N. Ya.

doi:10.1016/j.ejmech.2009.12.014

Cited by 80 publications

(40 citation statements)

References 24 publications

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“…Several compounds with related indeno[1,2-b]quinoline and indolo [2,3-b]quinoxaline nuclei have been reported as inhibitors of topoisomerases I and II (Deady et al, 1997(Deady et al, , 1999Chen et al, 2000) and as cytotoxic compounds (Shibinskaya et al, 2010). However, the main effect of topoisomerase inhibitors is cytotoxicity, which was not found with our compounds and probably rules out topoisomerase inhibitory activity for these oxime quinoxalines.…”

Section: Discussioncontrasting

confidence: 52%

Identification and Characterization of a Novel Class of c-Jun N-terminal Kinase Inhibitors

et al. 2012

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In efforts to identify novel small molecules with antiinflammatory properties, we discovered a unique series of tetracyclic indenoquinoxaline derivatives that inhibited lipopolysaccharide (LPS)-induced nuclear factor-B/activating protein 1 activation. Compound IQ-1 (11H-indeno[1,2-b]quinoxalin-11-one oxime) was found to be a potent, noncytotoxic inhibitor of pro-inflammatory cytokine [interleukin (IL)-1␣, IL-1␤, IL-6, IL-10, tumor necrosis factor (TNF)-␣, interferon-␥, and granulocyte-macrophage colony-stimulating factor] and nitric oxide production by human and murine monocyte/macrophages. Three additional potent inhibitors of cytokine production were identified through further screening of IQ-1 analogs. The sodium salt of IQ-1 inhibited LPS-induced TNF-␣ and IL-6 production in MonoMac-6 cells with IC 50 values of 0.25 and 0.61 M, respectively. Screening of 131 protein kinases revealed that derivative IQ-3 [11H-indeno[1,2-b]quinoxalin-11-one-O-(2-furoyl)oxime]was a specific inhibitor of the c-Jun N-terminal kinase (JNK) family, with preference for JNK3. This compound, as well as IQ-1 and three additional oxime indenoquinoxalines, were found to be high-affinity JNK inhibitors with nanomolar binding affinity and ability to inhibit c-Jun phosphorylation. Furthermore, docking studies showed that hydrogen bonding interactions of the active indenoquinoxalines with Asn152, Gln155, and Met149 of JNK3 played an important role in enzyme binding activity. Finally, we showed that the sodium salt of IQ-1 had favorable pharmacokinetics and inhibited the ovalbumin-induced CD4 ϩ T-cell immune response in a murine delayed-type hypersensitivity model in vivo. We conclude that compounds with an indenoquinoxaline nucleus can serve as specific small-molecule modulators for mechanistic studies of JNKs as well as a potential leads for the development of anti-inflammatory drugs.

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Section: Discussioncontrasting

confidence: 52%

Identification and Characterization of a Novel Class of c-Jun N-terminal Kinase Inhibitors

et al. 2012

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“…The high antiviral activity against Flu В was found for 6-[(β-diethylaminoethyl)thio]-3-phenyl-2H-[1,2,4]triazino [2,3-c]quinazoline-2-one (1.5). Its EC 50 was 1.1 mg/ml in the viral CPE test and 1.4 mg/ml in the increase and neutral red dye uptake increasing test (SI 50 [22][23][24]. The advanced tests conducted demonstrated higher effectiveness of Ribavirin (SI 50 100-530).…”

Section: Resultsmentioning

confidence: 99%

6-Thio-substituted-2h-[1,2,4]triazino[2,3-c]quinazolin-2-ones with the dialkylaminoethyl moiety – a new class of antivirial agents

et al. 2016

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“…Для пере-вірки цього припущення нами були синтезовані низки планарних сполук, що належать різним кла-сам конденсованих карбо-та гетероциклів і по-казано, що цим сполукам притаманні як інтер-каляція в ДНК, так і противірусна активність та здатність індукувати інтерферон [22,23]. Більше того, аналогічні результати були отримані інши-ми групами дослідників [24,25]. З іншого боку, похідні дифенілу 2, 3, синтезовані нами як такі, що скоріше за все не здатні до інтеркаляції, про-явили противірусні та інтерфероніндукуючі вла-стивості аналогічно аміксину [26,27], але ж, як і передбачалось, не інтеркалювали в ДНК (схема 1).…”

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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Synthesis, cytotoxicity, antiviral activity and interferon inducing ability of 6-(2-aminoethyl)-6H-indolo[2,3-b]quinoxalines

Cited by 80 publications

References 24 publications

Identification and Characterization of a Novel Class of c-Jun N-terminal Kinase Inhibitors

Identification and Characterization of a Novel Class of c-Jun N-terminal Kinase Inhibitors

6-Thio-substituted-2h-[1,2,4]triazino[2,3-c]quinazolin-2-ones with the dialkylaminoethyl moiety – a new class of antivirial agents

Synthesis and cytotoxicity of aminoethoxydiphenyls

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