научный журнал по химии Биоорганическая химия ISSN: 0132-3423

ГОРЮНОВА О. В., ЖУКОВА О. С., ЗАХАРЧУК Г. М., КУЗЬМИНА Н. Е., ФЕТИСОВА Л. В. — 2014 г.

В качестве потенциальных противоопухолевых агентов синтезированы N6-производные N12-рибозилиндоло[2,3-а]пирроло[3,4-с]карбазол-5,7-диона, в которых атом N6 пиррольной части гетероцикла включен в дипептидный остаток общей формулы >N6-(CH2)n-CO-Ala/ Ala-OMe (n = 2 или 3). Данные соединения получены путeм взаимодействия 13-метил-12-(2,3,4-три-О-ацетил-?-D-рибопиранозил)индоло[2,3-а]фурано[3,4-с]карбазол-5,7-диона с дипептидами, имеющими свободную N-концевую аминогруппу, в DMF при 130°С, при этом атом азота аминогруппы пептида замещает кислород О6 в фурановом кольце гетероцикла и встраивается в виде имидного атома азота пиррола N6. Изучена способность полученных соединений подавлять рост клеток карциномы яичников человека линии SKOV3, только производное с радикалом >N6-(СН2)3--L-Ala-ОМе проявило цитотоксическую активность с ингибирующей концентрацией IC50 = 8 мкМ.

HONG TAO REN, JUN YAN BAI, YONG HUANG — 2014 г.

piRNAs (piwi-interacting RNA) are a novel class of non-coding small single-stranded RNAs with the length of 26–33 nt. The piRNAs play important biological role through the specific interaction with the piwi proteins of the Argonaute family. piRNA function in embryonic development, maintenance of germline DNA integrity, silencing of transposon transcription, suppression of translation, formation of heterochromatin, and epigenetic regulation of sex determination. This review summarizes recent research and progress on biogenesis and function of piRNA ineukaryotic species.

KAHVECI B., KARAALI N., MENTESE E., ULKER S., YLMAZ F. — 2014 г.

This study presents a synthesis of new series of some benzimidazole, bisbenzimidazole and perimidine derivatives via microwave technique, which, leads to the good product yields and short reaction times. The structure of newly synthesized compounds was confirmed by 1H-NMR and 13C-NMR spectra. These compounds were screened for their lipase inhibition activity. Then, all compounds were evaluated with regard to pancreatic lipase activity, and some of the 2-substituted perimidines, bisperimidine and bisbenzimidazole derivatives showed lipase inhibition at various concentrations.

PANKAJ KUMAR CHAURASIA, SHASHI LATA BHARATI, SUNIL KUMAR SINGH — 2014 г.

Now a day, laccases are the most promising enzymes in the area of biotechnology and synthesis. One of the best applications of laccases is the selective oxidation of aromatic methyl group to aldehyde group. Such transformations are valuable because it is difficult to stop the reaction at aldehyde stage. Chemical methods used for such biotransformations are expensive and give poor yields. But, the laccase-catalyzed biotransformations of such type are non-expensive and yield is excellent. Authors have used crude laccase obtained from the liquid culture growth medium of fungal strain Coriolus versicolor MTCC-138 for the biotransformations of toluene, 3-nitrotoluene, and 4-chlorotoluene to benzaldehyde, 3-nitrobenzaldehyde, and 4-chlorobenz-aldehyde, respectively, instead of purified laccase because purification process requires much time and cost. This communication reports that crude laccase can also be used in the place of purified laccase as effective biocatalyst.

PANKAJ KUMAR CHAURASIA, SHASHI LATA BHARATI, SUDHA YADAVA, SUNIL KUMAR SINGH — 2014 г.

The chemical route of oxidation of methyl group to its aldehyde is inconvenient because once a methyl group is attacked, it is likely to be oxidized to the carboxylic acid and it is very difficult to stop the reaction at the aldehyde stage. Fungal laccases can be used for such oxidation reaction and the reaction can be completed sharply within 1–2 hrs. Coupling of amines are another important reactions known for fungal laccases; coupling reactions generally take 3–7 hrs. We have used the purified laccase of molecular weight 63 kDa obtained from the fungal strain Xylaria polymorpha MTCC-1100 with activity of 1.95 IU/mL for selective oxidation of 2-fluorotoluene, 4-fluorotoluene, and 2-chlorotoluene to 2-fluorobenzaldehyde, 4-fluorobenzaldehyde, and 2-chlorobenzaldehyde, respectively, and syntheses of 3-(3,4-dihydroxyphenyl)-propionic acid derivatives by N-coupling of amines. In each oxidation reactions, ABTS was used as mediator molecule. All the syntheses are ecofriendly and were performed at room temperature.

AMIN M. A., KHALIFA M. E. A., MOSSELHI M. A. N. — 2014 г.

Reaction of hydrazonoyl halides with 6-(benzylidenamino)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one and 2,3-diaminoquinazolin-4-one site-selectively afforded 3-substituted-7-(benzylidenamino)-1-phenyl-[1,2,4]triazolo[4,3-a]-pyrimidin-5(1H)-ones, [1,2,4,5]tetrazino[6,1-b]quinazolin-6(4H)-one, and 3-methyl-2-(4-substituted-phenylhydrazo)-[1,2,4]triazino[3,2-b]quinazolin-10-ones in good yields. The structures of the newly synthesized compounds were elucidated by chemical evidence and their IR, 1H, 13C NMR, and MS spectra. Furthermore, some of the products were screened against different strains of bacteria and fungi.

AL-OMAR MOHAMED A., AMR ABD EL-GALIL E., FAYED AHMED A., MOSTAFA ELSAYED E. — 2014 г.

A series of new 3-substituted-7-(2-chloro-6-ethoxypyridin-4-yl)-9-(2,4-dichlorophenyl)-2-methylpyrido[3,2:4,5]thieno[3,2-d]pyrimidin-4(3H)-one derivatives were synthesized as antimicrobial agents using 7-(2-chloro-6-ethoxypyridin-4-yl)-9-(2,4-dichlorophenyl)-2-methyl-4H-pyrido[3,2:4,5]thieno[3,2-d]-[1,3]oxazin-4-one as a starting compound. Its condensation with substituted aniline derivatives or phenyl hydrazine gave the corresponding N-substituted derivatives. Treatment of the starting compound with hydrazine hydrate afforded the corresponding N-amino derivative, which was reacted with substituted phenylisocyanate and phenylisothiocyanate derivatives to give the corresponding semicarbazides and thiosemicarbazide derivatives. All the newly synthesized compounds were evaluated for their antimicrobial activities in comparison to streptomycin and fusidic acid as positive controls. The structure assignments of the new compounds are based on chemical and spectroscopic evidence.

GIRISH V., GURUPADASWAMY H.D., NOOR FATIMA KHANUM, SHAUKATH ARA KHANUM — 2014 г.

Synthetic pathway of the ten novel 2-[2-(aroyl)aroyloxy]methyl-1,3,4-oxadiazoles as new potential antimicrobial agents is illustrated. Intramolecular cyclization of 2-(2-aroylaryloxy) aceto hydrazides to 2-[2-(aroyl)aroyloxy]methyl-1,3,4-oxadiazoles was achieved with triethyl orthoformate in good yields. The compounds were characterized by IR, 1H NMR, mass spectra and by means of CHN analysis. The target compounds were tested for their in vitro antimicrobial activity against representative strains by disc diffusion method and micro dilution methods. Several compounds showed antimicrobial activity comparable with or higher than the standard drugs.

LAKSHMI RANGANATHA V, SHAUKATH ARA KHANUM — 2014 г.

2,5-Disubstituted 1,3,4-oxadiazole compounds are one of the most attractive heterocyclic compounds for researchers due to their biological activities. In the undertaken research, a number of potential 2,5-disubstituted 1,3,4-oxadiazole analogues were synthesized through multi step reaction and characterized by FT-IR, 1H NMR, mass spectra, and also by elemental analysis. Further benzophenone tagged indole acetohydrazides and 2,5-disubstituted 1,3,4-oxadiazoles were evaluated for antioxidant potential, through different in vitro models such as DPPH, nitric oxide and hydrogen peroxide methods. In the series of compounds some of them had shown good to moderate in vitro antioxidant potential compare to the standard drug ascorbic acid in all the above three methods.

AL-OMAR MOHAMED A., KHALIFA NAGY M., NIELSEN CLAUS, PEDERSEN ERIK B. — 2014 г.

A novel series of uracil derivatives with a 3,5-dimethylbenzyl group at the C-6 position were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. Purity of the compounds has been confirmed by TLC. Structures of these compounds were established on the basis of elemental analyses and spectral studies. Some of the tested compounds showed moderate to potent activities against wild-type HIV-1, and N-1 alkylated derivatives were highly active.

BASAVARAJU Y.B., UMESHA B. — 2014 г.

The pyrazole analogues of podophyllotoxin were synthesized by the chalcone route. This route attracts the attention because of its simple operating conditions and easy availability of the chemicals. Initially, benzylideneacetophenones (chalcones) were prepared in high yields by Claisen-Schmidt reaction of acetophenones with 4-(methylthio)benzaldehyde. The cyclopropyl ketones were prepared in good yields by the reaction of chalcones with trimethylsulfoxonium iodide. Tetralones were prepared in good yields by the Friedel-Crafts intramolecular cyclization reaction of cyclopropyle ketones in the presence of anhyd. stannic chloride and acetic anhydride. The tetralones on formylation to give substituted hydroxylmethylene tetralones. Condensation of substituted hydroxylmethylene tetralones with hydrazine hydrate afforded target compounds. The structures of the synthesized compounds were confirmed by IR, 1H-NMR and Mass spectral technique. The title compounds were screened for their antimitotic and antimicrobial activities. Among the synthesized compounds cyclopropyl ketones and pyrazole analogues of podophyllotoxin, compound 7-(Methylthio)-5-(4-(methylthio)phenyl)-4,5-dihydro-2H-benzo[g]indazole is more active than 5-(4-(Methylthio)phenyl)-4,5-dihydro-2H-benzo[g]indazole, 7-Methyl-5-(4-(methylthio)phenyl)-4,5-dihydro-2H-benzo[g]indazole, 7-Methoxy-5-(4-(methylthio)phenyl)-4,5-dihydro-2H-benzo[g]indazole and the key intermediate tetralones in 100, 200 and 400 ppm at 12, 18 and 24 hrs and also showed very good activity against screened bacteria and fungi compared to their standard.

HARISH K. P., MALLESHA L., MOHANA K. N. — 2014 г.

A series of 2,5-disubstituted-1,3,4-thiadiazole derivatives were synthesized by the reaction of 3-(2-cyanopropan-2-yl)-N-(5-(piperazine-1-yl)-1,3,4-thiadiazol-2-yl)benzamide with various sulfonyl chlorides and evaluated for their anticonvulsant activity in MES test. Rotorod method was employed to determine the neurotoxicity. The purity of the compounds is confirmed on the basis of their elemental analysis. The structures of all the new compounds are established on the basis of 1H NMR and mass spectral data. Out of fifteen compounds, three were found to be potent anticolvunstants. The same compounds showed no neurotoxicity at the maximum dose administered (100 mg/kg).

YANNI AMAL S. — 2014 г.

Aromatic aldazines with thiocyanates in glacial acetic acid produce corresponding bistriazolidine derivatives via criss-cross cycloaddition reaction. The chemical structure was confirmed by elemental and spectral analysis. Biological activity against some microorganisms was tested.

AHMET DEMIRBAS, HACER BAYRAK, NESLIHAN DEMIRBAS, SENGUL ALPAY-KARAOGLU, SERDAR ULKER, SULE CEYLAN — 2014 г.

1,2,4-Triazole-3-one prepared from tryptamine was converted to the corresponding carbotioamides by several steps. Their treatment with ethyl bromoacetate or 4-chlorophenacyl bromide produced the corresponding 5-oxo-1,3-thiazolidine or 3-(4-chlorophenyl)-1,3-thiazole derivatives. Acetohydrazide derivative that was obtained starting from tryptamine, was converted to the corresponding Schiff basis and sulfonamide by the treatment with suitable aldehydes and benzensulphonyl chloride, respectively. 2-[(4-Amino-5-thioxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)methyl]-4-[2-(1H-indole-3-yl)ethyl]-5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-one was synthesized starting from hydrazide via the formation of the corresponding 1,3,4-oxadiazole compound, while the other bitriazole compounds were obtained by intramolecular cyclisation of carbothioamides in basic media. The treatment of 1,2,4-triazole or 1,3,4-oxadiazole compound with several amines generated the corresponding Mannich bases. Ethyl (2-amino-1,3-thiazole-4-yl)acetate was converted to the corresponding 1,3,4-oxadiazole derivative, arylidenehydrazides, 1,2,4-triazole-3-one and 5-oxo-1,3-oxazolidine derivatives by several steps. The structural assignments of new compounds were based on their elemental analysis and spectral (FT IR, 1H NMR, 13C NMR and LC-MS) data. The antimicrobial, antilipase and antiurease activity studies revealed that some of the synthesized compounds showed antimicrobial, antilipase and/or antiurease activity.

BULENT ALICI, CIDEM BILEN, ENGIN CETINKAYA, MERT OLGUN KARATAS, NAHIT GENCER, OKTAY ARSLAN — 2014 г.

1-Alkylbenzimidazole and 1,3-dialkyl benzimidazolium salts were synthesized and characterized by the data of IR, 1H NMR, 13C NMR spectra and elemental analyses. These compounds were investigated as tyrosinase inhibitors. Tyrosinase has been purified from banana by affinity chromatography on a Sepharose 4B gel conjugated with L-tyrosine-p-aminobenzoic acid. All the synthesized compounds inhibited the tyrosinase activity. Among the compounds studied, 1,4-di(1H-benzo[d]imidazol-1-yl)butane was found to be the most active tyrosinase inhibitor (IC50 0.31 mM).

ALY M.R.E., GHERBAWY Y. A. M. H., IBRAHIM M.M., OKAEL A.M. — 2014 г.

This paper describes the synthesis of a series of quinolines graphted with hydrazones, pyrazoles, pyridazine, phthalazine, triazepinone, semicarbazide, and thiomorpholide moieties and four metal complexes. These derivatives were screened against Fusarium oxysporum and the red palm weevil (RPW) Rhynchophorus ferrugineus Oliver (coleopteran: Curculionidae) as palm pathogens. Only chlorinated quinolines were active against these organisms with hydrazones being good fungicides, while those modified with pyrazoles and pyrazines showed moderate insecticidal activity. A unique trihydroxylated hydrazone was active against both organisms, while another hydrazone, the most potent fungicide in this series, exhibited insecticidal activity only upon complexation with Zn2+ ions.

ЗАЦЕПИНА О.В., КОРДЮКОВА М.Ю., ПОЛЗИКОВ М.А., ШИШОВА К.В. — 2014 г.

Белки семейства SURF6 – это эволюционно-консервативные белки “домашнего хозяйства” эукариот, однако функциональное значение SURF6 человека и его белковые партнеры до сих пор не установлены. В настоящей работе для ответа на эти вопросы мы использовали метод аффинной адсорбции (GST pull-down), а в качестве акцепторов – слитые с глутатион-S-трансферазой (GST) рекомбинантный SURF6 человека и рекомбинантный консервативный С-концевой домен Surf6 мыши (Surf6-dom мыши), имеющий 85% подобия с С-консервативным доменом SURF6 человека. Результаты работы показали, что GST-SURF6 в клетках человека HeLa взаимодействует c факторами процессинга рРНК (В23/нуклеофозмином, нуклеолином, EBP2), а также с кофактором РНК-полимеразы I, белком UBF. Эти же белковые партнеры связывались с GST-Surf6-dom. Данные наблюдения являются первыми экспериментальными свидетельствами в пользу участия SURF6 человека в биогенезе рибосом, включая транскрипцию рДНК и процессинг рРНК. Набор белковых партнеров GST-Surf6-dom в клетках HeLa указывает, кроме того, на возможное взаимодействие SURF6 человека c ядрышковыми и ядерными белками других функциональных групп, т.е. на его многофункциональность.

АНТИПОВ П.И., АНТИПОВА Т.А., ГУДАШЕВА Т.А., КУРИЛОВ Д.В., ЛОГВИНОВ И.О., ПОВАРНИНА П.Ю., САЗОНОВА Н.М., СЕРЕДЕНИН С.Б., ТАРАСЮК А.В. — 2014 г.

Ранее нами был получен димерный дипептидный миметик 4-й петли BDNF гексаметилендиамид бис(N-моносукцинил-L-серил-L-лизина) (ГСБ-106), обладающий нейропротективной активностью in vitro в интервале концентраций 10-5 10-8 М и антидепрессивной активностью in vivo в дозах 0.1 и 1 мг/кг внутрибрюшинно у крыс. В настоящей работе исследованы структурно-функциональные отношения в ряду аналогов ГСБ-106. Был проведен глициновый скан и синтезированы соответствующие соединения: ГТ-105 (замена Lys на Gly), ГТ-107 (замена Ser на Gly), ГТ-106Ac (замена Suc на Ac). Изучена зависимость активности от конфигурации аминокислотных остатков: ГТ-107D (D-энантиомер ГТ-107), ГТ-106DL (замена LSer на DSer), ГТ-106LD (замена LLys на DLys). Исследование этих соединений на клеточной культуре HT22 в условиях окислительного стресса показало сохранение нейропротективного эффекта при замене серина на глицин, замене сукцинильного радикала. Исчезновение эффекта наблюдалось при замене остатка лизина на глицин и D-лизин и обращении конфигурации серина. Полученные результаты свидетельствуют о ключевой роли бокового радикала лизина у ГСБ-106 в проявлении его нейропротективной активности. L-Конфигурация необходима как для остатка лизина, так и для остатка серина. В отсутствие бокового радикала серина конфигурация лизина остается критичной. Таким образом, минимальным нейропротективным фармакофором бета-изгиба 4-й петли BDNF является следующий фрагмент: HOOC CH2 CH2 CO NH (S)CH(CH2OH) CO NH (S)CH((CH2)4NH2) CO NH (CH2)3. Из двух аналогов ГСБ-106 с нейропротективной активностью антидепрессивной активностью обладает только ГТ-106Ас. Это свидетельствует о более строгих структурных требованиях для проявления антидепрессивной активности. Полученные результаты могут быть полезны для конструирования новой группы миметиков BDNF.

БЕЗБОРОДОВА О. А., ИВАНОВ В. Т., МИХАЛЕВА И. И., НЕМЦОВА Е. Р., ОНОПРИЕНКО Л. В., ПРУДЧЕНКО И. А., ЧИКИН Л. Д., ЯКУБОВСКАЯ Р. И. — 2014 г.

С целью изучения потенциальных возможностей применения аналогов пептида дельта-сна (DSIP) в онкологии синтезированы 16 пептидов, отличающихся по структуре от DSIP заменами 1–2 а.о. Исследованы антиоксидантные свойства пептидов in vitro и их детоксицирующая активность in vivo в модели токсикоза, вызванного цитостатиком цисплатином, широко применяемым в терапии опухолевых заболеваний. Показано, что практически все исследованные аналоги DSIP проявляют прямую антиоксидантную активность, причем аналог ID-6 обладал активностью более высокой, чем DSIP, и сравнимой с таковой для витамина С и ?-каротина. Данный аналог продемонстрировал также наиболее выраженный среди исследуемых пептидов детоксицирующий эффект по отношению к действию цисплатина, что проявлялось как в снижении до 17% гибели животных от острой токсичности, по сравнению с 50–67% в контроле, так и в улучшении ряда биохимических показателей крови – снижении активности ферментов аспартат- и аланинаминотрансфераз и концентрации конечных продуктов азотистого обмена: креатинина и мочевины. Таким образом, пептиды семейства DSIP могут оказаться перспективными средствами для снижения токсических эффектов цитостатиков, применяемых в онкологии.

БУРАВЛЕВ Е. В., КУЧИН А. В., ТОРЛОПОВ М. А., ЧУКИЧЕВА И. Ю., ШЕВЧЕНКО О. Г. — 2014 г.

Серия водорастворимых конъюгатов получена исходя из 4-бромометил-2,6-диизоборнилфенола и полиэтиленгликолей различной длины. Оценка мембранопротекторной и антиоксидантной активности синтезированных продуктов на модели Н2О2-индуцированного гемолиза эритроцитов показала, что конъюгаты обладают выраженной антиоксидантной активностью. Cущественный мембранопротекторный эффект выявлен у конъюгатов с массовым содержанием 2,6-диизоборнил-4-метиленовых фрагментов 0.2 и 0.8 масс. %.