1,2,4-Triazoloazine derivatives as a new type of herpes simplex virus inhibitors [Text] / S. L. Deev, M. V. Yasko, I. L. Karpenko, E. N. Ulomskii, O. N. Chupakhin // Bioorganic Chemistry . - 2010. - Vol. 38, № 6. - P265-270 Рубрики: ХИМИЧЕСКИЕ НАУКИ Аннотация: A new class of inhibitors of herpes simplex virus replication was found. The compounds under study are derived from condensed 1,2,4-triazolo[5,1-c][1,2,4]triazines and 1,2,4-triazolo[1,5-a]pyrimidines, structural analogues of natural nucleic bases. Antiherpetic activity and cytotoxicity of the compounds were studied. The corresponding triphosphates of several active compounds were prepared and tested as inhibitors of DNA synthesis catalyzed by herpes simplex virus polymerase. The potential mechanism of their action is blocking of DNA dependent DNA polymerase, a key enzyme of viral replication |
F 70 Fluorinated derivatives of benz[4,5]imidazo[2,1-b][1,3]thiazoles are inhibitors of measles viruses [Электронный ресурс] / A. G. Pokrovskii, E. A. Il"ichyova, S. K. Kotovskaya, S. A. Romanova, V. N. Charushin, O. N. Chupakhin // Doklady Akademii Nauk . - 2004. - Vol.398, №3. - P412-414 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): ANTIVIRAL ACTIVITY -- CYTOTOXICITY -- FLUORINATED BENZIMIDAZOLES Аннотация: The results of in vitro anti-virus activity investigation for the new benzimidazoles (their synthesis is reported previously) are presented. The activity of the most active compound was studied in dependence of its introduction to the culture (before virus adsorption, simultaneously with virus, directly after virus adsorption, after 6 hours and after 1 day). Preliminary treatment of cells didn't protect them from further infecting; therewith the compound introduction simultaneously with virus or after infection caused no considerable effect on its anti-virus activity. The latter is attributed to blocking of late stages of measles virus reproduction - synthesis or arrangement of virus proteins |
F 70 Fluorinated derivatives of Benz[4,5]imidazo[1,2-b][1,3] thiazole - Inhibitors of reproduction of measles virus [Электронный ресурс] / A. G. Pokrovskii, E. A. Il"ichyova, S. K. Kotovskaya, S. A. Romanova, V. N. Charushin, O. N. Chupakhin // Doklady Biochemistry and Biophysics . - 2004. - Vol.398, №1-6. - P285-287 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): RIBAVIRIN -- ANTIVIRAL AGENTS -- THIAZOLES |
A 23 Aerobic oxidative C-H/C-H coupling of azaaromatics with indoles and pyrroles in the presence of TiO2 as a photocatalyst [Electronic resource] / I. A. Utepova, M. A. Trestsova, O. N. Chupakhin, V. N. Charushin, A. A. Rempel // Green Chemistry. - 2015. - Vol. 17, № 8. - С. 4401-4410. - Bibliogr. : p. 4409-4410 (30 ref.) Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): BOND ACTIVATION -- INHIBITORS -- HYDROGEN Аннотация: In this paper we wish to report a highly selective and benign method for the double C-H/C-H coupling of azaaromatics with indoles or pyrrole in the presence of air oxygen/TiO2, as an effective photocatalytic oxidative system. It has been shown that this versatile approach can be applied for direct C-H functionalisation of a variety of azaaromatic systems, such as mono-, di- and triazines, substituted and unsubstituted azines and their benzo-annelated analogues. \\\\expert2\\nbo\\Green Chemistry\\2015, v.17, N 8, p.4401-4410.pdf |
A 37 Alkyl 2-arylhydrazinylidene-3-oxo-3-polyfluoroalkylpropionates as new effective and selective inhibitors of carboxylesterase [Electronic resource] / N. P. Boltneva, G. F. Makhaeva, N. V. Kovaleva, S. V. Lushchekina, Ya. V. Burgart, E. V. Shchegol’kov, O. N. Chupakhin // Doklady Biochemistry and Biophysics . - 2015. - Vol. 465, № 1. - С. 381-385. - Bibliogr. : p. 385 (15 ref.) Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): 2-ARYLHYDRAZINYLIDENE-3-OXO-3-POLYFLUOROALKYLPROPIONATES -- INHIBITORS -- CARBOXYLESTERASE Аннотация: A series of alkyl 2-Arylhydrazinylidene-3-oxo-3-polyfluoroalkylpropionates was synthesized and their inhibitory activity with respect to porcine liver carboxylesterase (CaE, EC 3.1.1.1), human erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7), and horse serum butyrylcholinesterase (BChE, EC 3.1.1.8) was studied. The molecular docking method was used to study the binding mode of the compounds in the active site of CaE. It was found that compounds containing the trifluoromethyl group in the third position of carbonyl chain are highly effective and selective inhibitors of CaE with nanomolar IC50 values, which agrees well with the results of molecular docking. Origin \\\\expert2\\nbo\\Doklady Biochemistry and Biophysics\\2015, v.465, № 1. p.381-385.pdf |
D 62 Direct Modification of Quercetin by 6-Nitroazolo[1,5-a]Pyrimidines [Electronic resource] / E. B. Gorbunov, G. L. Rusinov, E. N. Ulomskii, O. S. Eltsov, V. L. Rusinov, V. G. Kartsev, V. N. Charushin, I. A. Khalymbadzha, O. N. Chupakhin // Chemistry of Natural Compounds. - 2016. - Vol. 52, № 4. - С. 708-710 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): DERIVATIVES -- INHIBITORS -- ANALOGS \\\\expert2\\NBO\\Chemistry of Heterocyclic Compounds\\2016, v.52, N 4, p. 708-710.pdf |
S 98 Synthesis and antitumour activity of 4-aminoquinazoline derivatives [Electronic resource] / G. N. Lipunova, E. V. Nosova, V. N. Charushin, O. N. Chupakhin // Russian Chemical Reviews. - 2016. - Vol. 85, № 7. - С. 759-793 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): GROWTH-FACTOR RECEPTOR -- POTENT EGFR INHIBITORS -- TYROSINE KINASE INHIBITORS Аннотация: Scieces of data on the synthesis and antitumour activity of 4-aminoquinazolines are summarized and analyzed. Key methods for the synthesis of these compounds are considered, primarily cyclocondensation of carboxylic acid derivatives, as well as the oxidation of quinazolines and the cyclization of disubstituted thioureas. Improvements of synthetic schemes for erlotinib, gefitinib and lapatinib, which are the best-known pharmaceuticals based on compounds of the title class, are also considered. Synthetic strategies and biological activities for new 4-aminoquinazoline derivatives that are EGFR-tyrosine kinase inhibitors, multiactive compounds, and labelled compounds for use as positron emission tomography (PET) imaging agents are discussed. |
D 46 Design and Synthesis of N-Sulfonylamidines of Modafinic Acid [Electronic resource] / T. Beryozkina, V. A. Bakulev, L. Dianova, P. A. Slepukhin // Synthesis-Stuttgart. - 2016. - Vol. 48, № 7. - С. 1046-1054 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): MODAFINIL -- N-SULFONYL AMIDINES -- DAT INHIBITORS Аннотация: A design and a convenient approach for the synthesis of novel N-sulfonyl-2-diphenylmethylsulfinylacetamidines have been demonstrated by starting from benzhydrylsulfanylacetic (BSA) acid. This approach involves a sequential amidation with amines, thionation with Lawesson's reagent, iminosulfonylation with sulfonyl azides, and oxidation of sulfide fragment with hydrogen peroxide. The key step of this transformation (reaction of thioamides with sulfonyl azides) was carried out either in ethanol or in the absence of any solvent. The synthesized compounds were tested in cells for inhibition of dopamine transporter. Among the synthesized compounds, two products were found to be in a similar range of activity as the well-known dopamine transporter inhibitor, modafinil. \\\\expert2\\NBO\\Synthesis-Stuttgart\\2016. 48(7). 1046-1054.pdf |
C 51 Chemoenzymatic Synthesis of Modified 2′-Deoxy-2′-fluoro-β-d-arabinofuranosyl Benzimidazoles and Evaluation of Their Activity Against Herpes Simplex Virus Type 1 / M. I. Kharitonova, K. V. Antonov, I. V. Fateev, M. Ya. Berzina, S. K. Kotovskaya, V. N. Charushin // Synthesis (Germany). - 2017. - Vol. 49, № 5. - С. 1043-1052 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): CHEMOENZYMATIC SYNTHESIS -- BENZIMIDAZOLES -- HERPES SIMPLEX VIRUS TYPE 1 Аннотация: 1-(2′-Deoxy-2′-fluoro-β-d-arabinofuranosyl)benzimidazoles containing 4,6-difluoro-, 4,5,6-trifluoro-, 5-fluoro-6-methoxy-, and 5-methoxy-4,6-difluorobenzimidazole fragments were synthesized by using purine nucleoside phosphorylase-catalyzed chemoenzymatic approach. As expected, enzymatic synthesis of nucleosides proceeds in lower yields of target compounds in comparison with the synthesis of ribo- and 2′-deoxyribobenzimidazoles (40–55% vs 60–90%). The compounds obtained were tested against the herpes simplex virus type 1, by using the Vero E6 cells. 5-Methoxy-4,6-difluoro-1-β-d-(2′-deoxy-2′-fluoroarabinofuranosyl)benzimidazole did not show any antiviral activity, when used in nontoxic concentration. All other nucleosides proved to exhibit a selective antiherpes activity. In contrast, it was shown that benzimidazole-β-d-arabinofuranosides of both di- and trisubstituted derivatives, having substituents in positions 4–6 of the benzene ring, as well as unsubstituted compounds, cannot be synthesized by enzymatic transglycosylation. 1-(β-d-Arabinofuranosyl)benzimidazole was obtained through glycosylation of N-trimethylsilylbenzimidazole with 1-chloro-2,3,5-O-methoxymethyl-d-arabinose. The behavior of this compound, as inhibitor of purine nucleoside phosphorylase (PNP) E. сoli, was investigated. 1-(β-d-Arabinofuranosyl)benzimidazole was found to belong to a mixed type of inhibitors of PNP. This fact explains why all attempts to perform enzymatic arabinosylation of 4,6-di-, 5,6-di-, and 4,5,6-trisubstituted benzimidazoles failed \\\\expert2\\NBO\\Synthesis\\2017, v. 49(5), p. 1043-1052.pdf |
S 98 Synthesis and Evaluation of Novel [1,2,4]Triazolo[5,1-c][1,2,4]-triazines and Pyrazolo[5,1-c][1,2,4]triazines as Potential Antidiabetic Agents / V. L. Rusinov, I. M. Sapozhnikova, A. M. Bliznik, O. N. Chupakhin, V. N. Charushin, A. A. Spasov, P. M. Vassiliev, V. A. Kuznetsova, A. I. Rashchenko, D. A. Babkov // Archiv der Pharmazie. - 2017. - Vol. 350, № 5. - Pe1600361-[1]-e1600361-[15] Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): ANTIDIABETIC AGENTS -- ANTIGLYCATION -- AZOLOTRIAZINES -- CROSS-LINK BREAKERS -- DIABETES MELLITUS -- DIPEPTIDYL PEPTIDASE-4 INHIBITORS Аннотация: Inhibition of the dipeptidyl peptidase-4 (DPP4) enzyme activity and prevention of advanced glycation end (AGE) products formation represents a reliable approach to achieve control over hyperglycemia and the associated pathogenesis of diabetic vascular complications. In the frames of this research study, several triazolo- and pyrazolotriazines were synthesized and evaluated as inhibitors of AGE products formation, DPP4, glycogen phosphorylase and α-glucosidase activities, as well as AGE cross-link breakers. From the two considered classes of heterocyclic compounds, the pyrazolotriazines showed the highest potency as antiglycating agents and DPP4 inhibitors. Structure–activity relationships (SAR) for these compounds, which can be considered as potential drugs for the treatment of type 2 diabetes, were evaluated. \\\\Expert2\\NBO\\Archiv der Pharmazie\\2017 V 350 P.pdf |
9-substituted acridine derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors possessing antioxidant activity for alzheimer's disease treatment / G. F. Makhaeva [et al.] // Bioorganic and Medicinal Chemistry. - 2017. - Vol. 25, № 21. - P5981-5994 Рубрики: ХИМИЧЕСКИЕ НАУКИ |
S 98 Synthesis of new efficient and selective carboxylesterase inhibitors based on adamantyl and citronellyl 4,4,4-trifluoro-2-arylhydrazonylidene-3-oxobutanoates / N. A. Elkina, E. V. Shchegolkov, Ya. V. Burgart [et al.] // Russian chemical bulletin. - 2021. - Vol. 70, № 3. - P567–572 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): 4,4,4-TRIFLUORO-2-ARYLHYDRAZINYLIDENE-3-OXOBUTANOATES -- NATURAL ALCOHOLS -- CARBOXYLESTERASE -- INHIBITORS -- MOLECULAR DOCKING Аннотация: A series of new adamantyl and citronellyl 4,4,4-trifluoro-2-arylhydrazinylidene-3-oxo-butanoates was synthesized. The synthesized compounds in nanomolar concentrations selectively inhibit carboxylesterase, while their activity is independent of the nature and position of the substituent in the aryl fragment, which is consistent with the molecular docking results. |
D 46 Design and antioxidant properties of bifunctional 2H-imidazole-derived phenolic compounds-a new family of effective inhibitors for oxidative stress-associated destructive processes / E. L. Gerasimova, E. R. Gazizullina, M. V. Borisova [et al.] // Molecules. - 2021. - Vol. 26, № 21. - Ст. 6534 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): 2H-IMIDAZOLE -- POLYPHENOLS -- ANTIOXIDANT CAPACITY -- ANTIRADICAL CAPACITY Аннотация: The synthesis of inhibitors for oxidative stress-associated destructive processes based on 2H-imidazole-derived phenolic compounds affording the bifunctional 2H-imidazole-derived phenolic compounds in good-to-excellent yields was reported. In particular, a series of bifunctional organic molecules of the 5-aryl-2H-imidazole family of various architectures bearing both electron-donating and electron-withdrawing substituents in the aryl fragment along with the different arrangements of the hydroxy groups in the polyphenol moiety, namely derivatives of phloroglucinol, pyrogallol, hydroxyquinol, including previously unknown water-soluble molecules, were studied. The structural and antioxidant properties of these bifunctional 5-aryl-2H-imidazoles were comprehensively studied. The redox transformations of the synthesized compounds were carried out. The integrated approach based on single and mixed mechanisms of antioxidant action, namely the AOC, ARC, Folin, and DPPH assays, were applied to estimate antioxidant activities. The relationship “structure-antioxidant properties” was established for each of the antioxidant action mechanisms. The conjugation effect was shown to result in a decrease in the mobility of the hydrogen atom, thus complicating the process of electron transfer in nearly all cases. On the contrary, the conjugation in imidazolyl substituted phloroglucinols was found to enhance their activity through the hydrogen transfer mechanism. Imidazole-derived polyphenolic compounds bearing the most electron-withdrawing functionality, namely the nitro group, were established to possess the higher values for both antioxidant and antiradical capacities. It was demonstrated that in the case of phloroglucinol derivatives, the conjugation effect resulted in a significant increase in the antiradical capacity (ARC) for a whole family of the considered 2H-imidazole-derived phenolic compounds in comparison with the corresponding unsubstituted phenols. Particularly, conjugation of the polyphenolic subunit with 2,2-dimethyl-5-(4-nitrophenyl)-2H-imidazol-4-yl fragment was shown to increase ARC from 2.26 to 5.16 (104 mol-eq/L). This means that the considered family of compounds is capable of exhibiting an antioxidant activity via transferring a hydrogen atom, exceeding the activity of known natural polyphenolic compounds. |
Combined in silico, ex vivo, and in vivo assessment of L-17, a thiadiazine derivative with putative neuro-and cardioprotective and antidepressant effects / A. Sarapultsev, P. M. Vassiliev, D. M. Grinchii [et al.] // International journal of molecular sciences. - 2021. - Vol. 22, № 24. - P13626 Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): TREATMENT-RESISTANT DEPRESSION -- POST-STROKE DEPRESSION -- C-FOS IMMUNOHISTOCHEMISTRY -- BINDING AFFINITY Аннотация: Depression associated with poor general medical condition, such as post-stroke (PSD) or post-myocardial infarction (PMID) depression, is characterized by resistance to classical antidepressants. Special treatment strategies should thus be developed for these conditions. Our study aims to investigate the mechanism of action of 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide (L-17), a recently designed thiadiazine derivative with putative neuro- and cardioprotective and antidepressant-like effects, using combined in silico (for prediction of the molecular binding mechanisms), ex vivo (for assessment of the neural excitability using c-Fos immunocytochemistry), and in vivo (for direct examination of the neuronal excitability) methodological approaches. We found that the predicted binding affinities of L-17 to serotonin (5-HT) transporter (SERT) and 5-HT3 and 5-HT1A receptors are compatible with selective 5-HT serotonin reuptake inhibitors (SSRIs) and antagonists of 5-HT3 and 5-HT1A receptors, respectively. L-17 robustly increased c-Fos immunoreactivity in the amygdala and decreased it in the hippocampus. L-17 dose-dependently inhibited 5-HT neurons of the dorsal raphe nucleus; this inhibition was partially reversed by the 5-HT1A antagonist WAY100135. We suggest that L-17 is a potent 5-HT reuptake inhibitor and partial antagonist of 5-HT3 and 5-HT1A receptors; the effects of L-17 on amygdaloid and hippocampal excitability might be mediated via 5-HT, and putatively mediate the antidepressant-like effects of this drug. Since L-17 also possesses neuro- and cardioprotective properties, it can be beneficial in PSD and PMID. Combined in silico predictions with ex vivo neurochemical and in vivo electrophysiological assessments might be a useful strategy for early assessment of the efficacy and neural mechanism of action of novel CNS drugs. |
Polyfluoroalkyl-2-hydroxyimino-1,3-diketones as new selective carboxylesterase inhibitors / N. P. Boltneva, S. V. Lushchekina, O. G. Serebryakova [и др.] // MedChem-Russia 2021: материалы 5-ой Российской конференции по медицинской химии с международным участием. - Волгоград, 2021. - С. 256 Рубрики: ХИМИЧЕСКИЕ НАУКИ |
Multitarget agents for the treatment of alzheimer's disease based on cholinesterase inhibitors / G. F. Makhaeva, N. V. Kovaleva, S. V. Lushchekina [и др.] // MedChem-Russia 2021: материалы 5-ой Российской конференции по медицинской химии с международным участием. - Волгоград, 2021. - С. 59 Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): INHIBITORS CHOLINESTERASE |
3-(2-Arylhydrazono)-1,1,1-trifluro-3-(phenylsulfonyl)propan-2-ones as selective carboxylesterase inhibitors / E. V. Shchegolkov, Y. V. Burgart, N. A. Elkina [et al.] // Russian chemical bulletin. - 2022. - Vol. 71, № 1. - P158-164 Рубрики: ХИМИЧЕСКИЕ НАУКИ Аннотация: We improved the synthetic procedure for 3-(2-arylhydrazono)-1,1,1-trifluro-3-(phenylsulfonyl)propan-2-ones and established their structure. The study of their esterase profile showed the absence of cholinesterase inhibition and the selectivity against carboxylesterase with micromolar activity exceeding the anticarboxylesterase activity of the diketone analog. Carboxylesterase inhibition data are consistent with molecular docking results. 3-(2-Arylhydrazono)-1,1,1-trifluro-3-(phenylsulfonyl)propan-2-ones exhibit a high radical-scavenging effect in the ABTS test exceeding that of Trolox. |
Antiviral properties of verdazyls and leucoverdazyls and their activity against group b enteroviruses / A. S. Volobueva, V. V. Zarubaev, T. G. Fedorchenko [et al.] // Russian journal of infection and immunity. - 2023. - Vol. 13, № 1. - P107-118 Рубрики: ХИМИЧЕСКИЕ НАУКИ ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): ENTEROVIRUSES -- ENTEROVIRAL INFECTION -- COXSACKIEVIRUS Аннотация: Enteroviruses are non-enveloped viruses of Enterovirus genus, Picornaviridae family, causing a variety of human diseases: from acute respiratory and intestinal infections to more severe pathologies including poliomyelitis, encephalitis, myocarditis, pancreatitis. Currently, no approved direct-acting antiviral drugs for treatment of enterovirus infections exists, whereas vaccination is available only for prevention of poliomyelitis and enterovirus 71 infection. Therefore, it is promising to conduct a search for inhibitors of enteroviruses life cycle in drug development to treat enterovirus infections. Here, antiviral properties of stable free radicals, verdazyls, and their precursors, leucoverdazyls, were investigated. It has been shown that leucoverdazyls vs verdazyls increased the survival of permissive cell culture infected with coxsackievirus. The activity range of the lead leucoverdazyl against RNA-containing and DNA-containing human viruses (in the viral yield reduction assay) and its proposed mechanism of action (time of addition assay) was studied. The lead compound suppressed reproduction of group B enteroviruses in vitro, with modest activity against influenza A virus and no activity against herpes virus type 1 and adenovirus type 5. The maximum decrease in viral titers was observed upon its addition to infected cells during early and middle stages of the virus life cycle. Thus, we concluded that the studied compound has a pronounced inhibitory activity against group B enteroviruses not belonging to the class of capsid binder inhibitors, without virucidal properties. Previously, we described antioxidant properties of leucoverdazyls. It is known that many viral infections are accompanied by production of reactive oxygen species and oxidative stress, and some compounds with antioxidant properties exhibit antiviral potential. Targeted chemical modifications of leucoverdazyls and further studies of leucoverdazyl mechanism of action as well as in vivo animal studies are needed. However, the results obtained may be useful for future development of new antiviral drugs to treat enteroviral infections. |