научный журнал по химии Биоорганическая химия ISSN: 0132-3423

ABDULRAZZAQ ABDULLAH Y., KAMAL EL-DEAN ADEL M., ZAKI REMON M. — 2015 г.

A new method for synthesizing 4-amino-3-methyl-1-phenyl-1H-5-substituted thieno[2,3-c]pyrazole was reported. The substituted groups at position 5 include carbonitrile, carboxamide, N-phenyl carboxamide, and benzoyl groups. The newly synthesized compounds and their derivatives were characterized by elemental analysis and spectroscopy (IR, 1H NMR, and mass spectra). Furthermore, some of these synthesized compounds were screened against various pathogenic bacterial and fungal strains. The results demonstrate that most of the synthesized compounds possess a significant antibacterial activity against gram-positive and gram-negative bacteria. In addition, most of these compounds showed a remarkable anti-fungal activity. On the other hand, some of the synthesized compounds possess high anti-inflammatory activity, which was demonstrated using the carrageenan-induced rat paw edema assay.

KI HWAN LEE, MUHAMMAD HANIF, MUHAMMAD RAFIQ, MUHAMMAD SALEEM, QAMAR ABBAS, SUNG-YUM SEO — 2015 г.

A series of aralkanoic acids was converted into aralkanoic acid hydrazides through their esters formation. The aralkanoic acid hydrazides upon treatment with carbon disulfide and methanolic potassium hydroxide yielded potassium dithiocarbazinate salts, which on refluxing with aqueous hydrazine hydrate yielded 5-aralkyl-4-amino-3-mercapto-1,2,4-triazoles. The target compounds, 3-aralkyl-6-(substitutedquinolinyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles, were synthesized by condensing various quinolinyl substituted carboxylic acids with 5-aralkyl-4-amino-3-mercapto-1,2,4-triazoles in phosphorus oxychloride. The structures of the newly synthesized triazolothiadiazoles were characterized by IR, 1H NMR, 13C NMR, and elemental analysis studies. The structure of one of the 5-aralkyl-4-amino-3-mercapto-1,2,4-triazoles was unambiguously deduced by single crystal X-ray diffraction analysis. All the synthesized compounds were screened for their acetylcholinesterase inhibition activities. Four of the triazolothiadiazoles exhibited excellent acetylcholinesterase inhibition activities as compared to the reference inhibitor.

ABDULLA MOHAMED M., AL-OMAR MOHAMED A., AMR ABD EL-GALIL E., HUSSAIN AZZA A., SHALABY AHMED F. A. — 2015 г.

A series of substituted (pyridin-4-yl)phenyl-2-methoxybenzamide and their derivatives were prepared and screened for their anti-inflammatory activities. Initially the acute toxicity of the compounds was assayed via the determination of their LD50. Some of the newly synthesized compounds exhibited better pharmacological and biological responses than the reference controls with low concentrations. The structures of newly synthesized compounds were confirmed by chemical, elemental and spectroscopic evidences.

HONG TAO REN, XI HONG SUN, YONG HUANG, ZHAN BIN WANG — 2015 г.

MicroRNAs (miRNAs) are a group of endogenous, short non-coding RNAs with the length of about 22 nt, which mediate gene expression at the post-transcriptional level through mRNA degradation or translational repression. Among them, some are highly evolutionally conserved in the animal kingdom; this provides a powerful strategy for identifying miRNAs in new species. The Chinese soft-shelled turtle (Pelodiscus sinensis) is one of the most important freshwater aquaculture reptilian species in China, but related miRNAs have not been identified up to now. In the present study, a total of 10 Pelodiscus sinensis miRNAs were identified according to Pelodiscus sinensis ESTs and GSSs information in NCBI database by bioinformatics approaches. The RT-PCR-based assays were performed and found that 10 Pelodiscus sinensis miRNAs were expressed. Using these miRNAs, 22 target genes were identified. These genes encode 22 proteins involved in metabolism, signal transduction, transcriptional regulation, and development. These miRNAs and their targets will serve as useful resources for their functional analyses in miRNA-regulated processes in Pelodiscus sinensis breeding and genetic research.

ABDEL-HAFEZ SH. H., EL AZAB I.H. — 2015 г.

New 2-methyl-5-(4-oxo-2-(substituted phenyl)thiazolidin-3-yl)thieno[3,4-d]-pyrimidin-4-one, 5-(2,7-diphenyl-5-thioxo-5,6,7,7a-tetrahydrothiazolo[4,5-d]pyrimidin-3(2H)-yl)-2-methylthieno[3,4-d]pyrimidin-4(3H)-one, and 2-methyl-5-(5-phenyl-thiazolo[5,4-d]isoxazol-6(5H)-yl)thieno[3,4-d]pyrimidin-4(3H)-one have been prepared under microwave-assisted and conventional conditions. The new compounds were screened for their in vitro antimicrobial activity against two gram-positive bacteria (Bacillus subtilis NCIM-2063 and Staphylococcus aureus NCIM-2901), one gram-negative bacteria (Escherichia coli NCIM-2256), and three fungal strains (Candida albicans NCIM-3471, Aspergillus flavus NCIM-539, and Aspergillus niger NCIM-1196) and showed promising biological activity.

КОРНЕЕНКО Т.В., МОДЯНОВ Н.Н., ОККЕЛЬМАН И.А., ПЕСТОВ Н.Б., ШАХПАРОНОВ М.И. — 2015 г.

Р4-ATP-азы – чрезвычайно интересное семейство среди ATP-аз Р-типа, поскольку их основная функция – перенос фосфолипидов, в частности фосфатидилсерина, из наружного монослоя мембраны во внутренний. Изоформы Р4-ATP-аз в определенной степени взаимозаменимы, но особенности тканеспецифичной экспрессии их генов, а также внутриклеточной локализации белков и путей их регуляции приводят к тому, что при нарушении структуры определенных изоформ на уровне целого организма могут развиваться достаточно тяжелые патологические состояния. Среди Р4-ATP-аз особое место занимает продукт гена ATP8B1, так как для этого гена известен ряд точечных мутаций, которые вызывают тяжелые наследственные заболевания: две формы наследственного холестаза (болезнь Байлера и доброкачественный рецидивирующий внутрипеченочный холестаз) с экстрапеченочными симптомами, такими как нейросенсорная глухота, пневмония, нарушение работы потовых желез, отставание в развитии. Физиологическая функция белка Atp8b1/FIC1 известна в общих чертах – он отвечает за транспорт некоторых фосфолипидов (фосфатидилсерин, кардиолипин) из наружного монослоя плазматической мембраны во внутренний. Хорошо установлено, что нарушение асимметрии мембраны из-за недостаточной активности Atp8b1/FIC1 приводит к гибели волосковых клеток внутреннего уха, нарушению транспорта желчных кислот в клетках печени и развитию цирроза. Вероятно также, что недостаточная активность Atp8b1/FIC1 предрасполагает и к повышенной чувствительности к бактериальным инфекциям. Нужно отметить, что до сих пор недостаточно изучены пути регуляции активности Atp8b1/FIC1 in vivo. Это предполагает перспективность исследований данного белка с целью лучшего понимания молекулярных процессов, предопределяющих развитие патологий и выявления новых потенциальных терапевтических мишеней.

ALI SHIRI, HODA ATAPOUR-MASHHAD, MARZIEH AKBARZADEH, MEHDI BAKAVOLI, SEYED-HADI MOUSAVI, ZAHRA TAYARANI-NAJARAN — 2015 г.

In vitro antiproliferative activities of some pyrimido[4,5-e][1,3,4]oxadiazine and [1,2,4]triazolo[4,3:1,2]pyrimido[4,5-e][1,3,4]oxadiazine derivatives were examined in human malignant cancer cell lines. All synthesized compounds inhibited the growth of malignant cells in a dose dependent manner, but among them 1,5,7-trimethyl-3-phenyl-1H-[1,2,4]triazolo[4,3:1,2]pyrimido[4,5-e][1,3,4]oxadiazine and [(1,5-dimethyl-3-phenyl-1H-[1,2,4]triazolo[4,3:1,2]pyrimido[4,5-e][1,3,4]oxadiazin-7-yl)sulfanyl]acetonitrile, both with triazole moiety, were found to be more effective than other compounds; they also induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to controls, indicating that apoptotic cell death is involved in toxicity they induce. The results showed that compounds with triazole moiety fused to pyrimido[4,5-e][1,3,4]oxadiazine derivatives are more active than those bearing chlorine or pyrrolidine groups at C-7 position.

AL-GHORBANI M., KHANUM S.A., LAKSHMI RANGANATHA V., PRASHANTH V., REKHA N.D., VEERABASAPPAGOWDA T. — 2015 г.

A series of novel piperazine analogues bearing quinolin-8-yloxy-butan-1-ones/pyridin-2-yloxy-ethanones were synthesized by a simple and convenient approach based on various substituted piperazine incorporating quinoline and pyridine moieties. The analogues were evaluated for in vitro antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferrous ion radical scavenging activities and anti-inflammatory activity by inhibition of Vipera russelli venom (PLA2) and gastric K+/H+-ATPase activities. Most of the title compounds exhibited promising activity. Best antioxidant and PLA2-inhibiting activities were found for piperazine analogues with phenyl and nitro phenyl groups, whereas methoxy group on phenyl piperazine indicated selectivity for the H+/K+-ATPase.

BOJA POOJARY, HIMANSHU JOSHI, MUMTAZ MOHAMMED HUSSAIN, PRATHIBHA A., REVANASIDDAPPA B.C., SHRUTHI N., VASANTHA KUMAR — 2015 г.

A new series of N-Aryl-2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)acetamides were synthesized by condensation of tricyclic compound 2,5-dihydro-3H-[1,2,4]triazino[5,6-b]indole-3-thione with chloro N-phenylacetamides. The tricyclic compound was obtained by condensation of Isatin with thiosemicarbazide. Chloro N-phenylacetamides were obtained from different substituted anilines. Their structures were characterized by IR, 1H NMR, LC-MS and elemental analyses. Newly synthesized compounds were screened for antimicrobial, antidepressant and anticonvulsant activities. Preliminary results indicated that most of the compounds showed lesser MIC value than the standard drug used when tested for antimicrobial activity. Some of the compounds were endowed with very good antidepressant and anticonvulsant activity.

JAISHREE V., KUMAR PATIL, RANDIVE K.H., SANTOSH PATIL K. — 2015 г.

Coumarins have been isolated from plants and reported for antioxidant properties. In the present study, we report synthesis of new coumarin derivatives as prospective therapeutic agents and investigate their antioxidant properties.

ABDEL-RAHMAN REHAB F., AL-OMAR MOHAMED A., AMR ABD EL-GALIL E., BAIUOMY AYMAN R., KHALIFA NAGY M. — 2015 г.

Some novel bicyclic thiazolopyrimidine derivatives bearing various substituents have been synthesized through one-pot three-component method. Structures of the target compounds were confirmed by elemental analysis and spectral data. Some selected members of the newly synthesized compounds were investigated for their analgesic and anti-inflammatory activities and revealed pronounced anti-inflammatory activity greater than that of indomethacin (reference drug).

WU J.R., ZHAN X.B., ZHANG H.T., ZHENG Z.Y. — 2015 г.

A novel hydrogel was prepared from polysialic acid (PSA) and carboxymethyl chitosan (CMCS) using glutaraldehyde as the cross-linking agent. The resulting PSA–CMCS hydrogel exhibited pH sensitivity, in which the swelling ratio under acidic conditions was higher than those under neutral or alkaline conditions. The swelling ratio of PSA–CMCS hydrogel at equilibrium depended on the medium pH, the cross-linking agent concentration, and the ratio of PSA to CMCS (w/w). Bovine serum albumin (BSA) and 5-fluorouracil (5-FU) were used as model drugs to prepare hydrogel delivery systems. The loading efficiencies of the hydrogel for BSA and 5-FU were 26.25 and 36.74%, respectively. Release behaviors of BSA and 5-FU were influenced by the pH. MTT assays confirmed that PSA–CMCS hydrogel has no cytotoxicity toward the NIH-3T3 cell line; in fact, the 100% aqueous extract of the PSA–CMCS hydrogel enhanced cell growth. These results suggest that PSA–CMCS hydrogel may be a promising pH-sensitive delivery system, especially for hydrophobic chemicals.

CIDEM BILEN, MUSTAFA ARSLAN, NAHIT GENCER, NURCAN BERBER, OKTAY ARSLAN, ZUBEYDE SACKES — 2015 г.

A new series of phthalazine substituted -lactam derivatives were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase (hCA I and II) were evaluated. 2H-Indazolo[2,1-b]phthalazine-trione derivative was prepared with 4-nitrobenzaldehyde, dimedone, and phthalhydrazide in the presence of TFA in DMF, and the nitro group was reduced to 13-(4-aminophenyl)-3,3-dimethyl-3,4-dihydro-2H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione with SnCl2 · 2H2O. The reduced compound was reacted with different aromatic aldehydes, and phthalazine substituted imines were synthesized. The imine compounds undergo (2+2) cycloaddition reactions with ketenes to produce 2H-indazolo[2,1-b]phthalazine-trione substituted -lactam derivatives. The -lactam compounds were tested as inhibitors of the CA isoenzyme activity. The results showed that all the synthesized compounds inhibited the CA isoenzyme activity. 1-(4-(3,3-dimethyl-1,6,11-trioxo-2,3,4,6,11,13-hexahydro-1H-indazolo[1,2-b]phthalazin-13-yl)phenyl)-2-oxo-4-p-tolylazetidin-3-yl acetate (IC50 = 6.97 for hCA I and 8.48 for hCA II) had the most inhibitory effect.

CHIKHALIA K.H., LAKUM H.P., SHAH D.R. — 2015 г.

In frames of the search for new biological entities to fight against recent drug-resistant microbial strains, we report a library of quinazoline-based thiourea/4-thiazolidinone/chalcone hybrids. The newly synthesized compounds were studied for efficacy against several bacteria (Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Klebsiella pneumoniae) and fungi (Candida albicans and Aspergillus clavatus) using the broth dilution technique. From the biological evaluation, (E)-3-(3,4-dimethoxyphenyl)-1-(4-((4-(4-ethylpiperazin-1-yl)quinazolin-2-yl)amino)phenyl)prop-2-en-1-onewas found to be the most active analogue (microbial inhibition concentration 3.12 ) to inhibit the bacterial growth. The rest of the compounds showed equipotent efficacy (3.12 12.5 ) as compared to the standard. Final compounds were characterized by FT-IR, 1H NMR, 13C NMR, mass spectroscopy, and elemental analysis.

EL AZAB ISLAM H., KHALED KHALED M. — 2015 г.

The synthesis of the multifunctional, hitherto unreported 3-(3-(dimethylamino)acryloyl)-2H-naphtho[1,2-b][1,4]oxazin-2-one was described and its utility as a versatile building block was demonstrated for the synthesis of some new pyrimidines, pyrazoles, isoxazoles, pyrazolo[a]pyrimidines, triazolo[a]pyrimidines, pyrido[d]pyrimidines, pyrido[d]pyrimidines, piperidines, pyrido[a]benzimidazoles, 2H-pyran-3-carboxamides, benzofurans, naphtho[b]furans and pyrazolo[c][1,2,4]triazines of potential biological activities. The synthesized compounds were characterized by IR, 1H NMR, 13C NHR and mass spectral data. Some of the compounds were evaluated for antimicrobial activities.

ABDEL HAFEZ S.H., ALY M.R.E., GOBOURI A.A., SAAD H.A. — 2015 г.

Thienyl–triazine–sulphonamide conjugates were prepared from their precursor amines using triethyl orthoformate or ethyl chloroformate as cross coupling reagents. The progress of these reactions was investigated by spectral (IR, NMR, MS) and microanalytical techniques. The synthesized compounds were in vitro screened for antibacterial, antifungal, antioxidant, and anticancer activity. 4-[({[3-Mercapto-5-oxo-6-[2-(2-thienyl)vinyl]-1,2,4-triazin-4(5H)-yl]imino}methyl)amino]-benzenesulfonamide turned out to be a powerful antibacterial agent, while all the compounds prepared were inactive against fungal species tested. 4-{[({8-Cyano-4-oxo-3-[2-(2-thienyl)vinyl]-4H,8H-[1,2,4]triazino[3,4-b][1,3,4]thiadiazin-7-yl}amino)(ethoxy)methyl]amino}benzenesulfonamide displayed in vitro promising cytotoxicity against Ehrlich ascites carcinoma cell line with concurrent attenuation of malonodinitrile and it was unique among other compounds being unable to increase glutathione S-transferase and reduced glutathione S-transferase activities. This compound exhibited also good antioxidant properties that together with its cytotoxicity nominated it for further investigation in cancer research.

АДАМОВА И.Ю., АЗЬМУКО А.А., АФАНАСЬЕВА М.И., АФАНАСЬЕВА О.И., КОТКИНА Т.И., ЛЕВАШОВ П.А., ОВЧИННИКОВА Е.Д., ПОКРОВСКИЙ С.Н., ФРИД Д.А. — 2015 г.

Получены гемосовместимые аффинные сорбенты на основе полисахаридной матрицы и лигандов – пептидов WY, WTY, WNY, связывающиe иммуноглобулины G человека (IgG). Проведено сравнение характеристик сорбентов по связыванию как общего IgG так и подклассов IgG. Обнаружено, что все новые сорбенты имеют хорошие характеристики по удалению IgG из плазмы крови, но сорбент на основе WNY в полтора раза эффективней остальных связывает IgG подкласса 3 (IgG3). Определены физико-химические характеристики процесса связывания IgG. Для сорбентов на основе пептидов WY, WTY, WNY константы десорбции IgG составили 10 ± 3, 28 ± 4 и 13 ± 3 мкМ. Максимальная расчетная сорбционная емкость по IgG составила 43 ± 2, 45 ± 3 и 46 ± 3 мг IgG на 1 мл сорбента. Показана гемосовместимость сорбентов, пригодность для медицинского использования.

АНДРЕЕВ Я.А., БЕЛОЗЕРОВА О.А., ГРИШИН Е.В., КОЗЛОВ С.А., КОШЕЛЕВ С.Г., КУБЛИЦКИЙ В.С., ОСМАКОВ Д.И. — 2015 г.

Ранее из чабреца Thymus armeniacus был выделен новый лигнан – севанол, установлена его структура и показано, что он эффективно ингибирует работу кислоточувствительного канала ASIC3, а также проявляет ярко выраженное анальгетическое и противовоспалительное действие. В рамках данной работы в электрофизиологических экспериментах на человеческих ASIC3 каналах, экспрессированных в ооцитах Xenopus laevis, была измерена биологическая активность аналога севанола, полученного химическим синтезом, его стереоизомера и соединения-предшественника, молекула которого представляет собой половину молекулы севанола. Измеренная ингибирующая активность синтетического аналога совпала с активностью природного образца, стереоизомер показал падение ингибирующей активности примерно на треть, а предшественник был еще менее эффективным ингибитором. Таким образом, была показана значимость функциональных групп и пространственной конфигурации севанола для его биологической активности, что важно учитывать при планировании оптимального метода его синтеза и разработке лекарственных препаратов на его основе.

АНДРИАНОВА А.Г., АРХИПОВА В.А., ДУБОВЦЕВА Е.С., КУДЖАЕВ А.М., РОТАНОВА Т.В., СЕРОВА О.В. — 2015 г.

АТР-зависимая LonА-протеаза из E. coli (Ес-Lon), относящаяся к суперсемейству ААА+-белков, является ключевым участником системы контроля качества клеточного протеома. Ес-Lon функционирует как гомогексамер и расщепляет аномальные и дефектные полипептиды, а также ряд регуляторных белков по процессивному механизму. Субъединица Ес-Lon включает АТР-азный и протеолитический компоненты (ААА+-модуль и Р-домен), а также уникальную для ААА+-белков некаталитическую область, образованную N-концевым (N) и инсерционным -спирализованным (HI(СС)) доменами. С целью выявления роли HI(СС)-домена в функционировании фермента получены мутанты Ес-Lon с заменами остатков R164, R192 и Y294, локализованных в этом домене, и изучены их свойства. Показано, что С-концевая часть НI(СС)-домена аллостерически влияет на эффективность функционирования АТР-азного и протеолитического центров фермента, а его coiled-coil(СС)-область вовлечена во взаимодействие с белковым субстратом.

ИВАНОВ Р.А., ЛЕВАШОВ П.А., СМИРНОВ С.А., СОБОЛЕВА О.А. — 2015 г.

Изучено влияние поверхностно-активных веществ (ПАВ) различной природы: анионного (додецилсульфат натрия, SDS), катионного (бромид додецилтриметиламмония, DTAB) и цвиттер-ионного (кокоамидопропил бетаин, CAPB) – на лизис грамположительных бактерий Micrococcus luteus под действием яичного лизоцима при рН 7.2 и ионной силе раствора 0.15 М. Установлено, что при малых концентрациях SDS и DTAB (менее 10-5 М) происходит рост бактериолитической активности лизоцима на 30–140%. При более высоких концентрациях (10-5 10-4 М) активность снижается до значений, полученных в отсутствие ПАВ. Рост активности соотнесен с формированием гидрофобных комплексов лизоцим–ПАВ. При добавлении САРВ в концентрации свыше 10-5 М лизис M. luteus существенно замедляется, что связано с агрегированием лизоцима под действием САРВ.