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1.
Shigeru Moriyama Satoru Kataoka Kazuhiro Nakanishi Ryuichi Matsuno Tadashi Kamikubo 《Bioscience, biotechnology, and biochemistry》2013,77(11):2737-2739
N-(1-Arylethenyl)-2-chloroacetamides were synthesized and their herbicidal activities were tested. Among them, both 2-chloro-N-(2-methoxyethyl)-N-(2-methyl-1-phenylpropen-1-yl)acetamide and 2-chloro-N(2-ethoxyethyl)-N-(2-methyl-1-phenylpropen-1-yl)acetamide were found to be highly active against upland weeds. 相似文献
2.
Pascal Marchand Maud Antoine Guillaume Le Baut Michael Czech Silke Baasner Eckhard Günther 《Bioorganic & medicinal chemistry》2009,17(18):6715-6727
The synthesis and study of the structure–activity relationships of cytotoxic compounds based on N-pyridinyl or N-aryl-2-(1-benzylindol-3-yl)glyoxamide skeleton, represented by the lead structures D-24241 and D-24851, are described. The presence of N-(pyridin-4-yl) moiety was crucial for activity and 2-[1-(4-chloro-3-nitrobenzyl)-1H-indol-3-yl]-2-oxo-N-(pyridin-4-yl)acetamide (55), the most potent derivative, showed IC50 = 39 nM, 51 nM and 11 nM against HeLa/KB (human cervix carcinoma), L1210 (murine leukemia) and SKOV3 (human ovarian carcinoma) cell lines proliferation assay, respectively, as active as the lead compounds. 相似文献
3.
MARC LE BORGNE PASCAL MARCHAND MARIE-RENEE NOURRISSON DENIS LOQUET MARTINA PALZER GUILLAUME LE BAUT 《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):667-676
This present study identifies a number of azolyl-substituted indoles as potent inhibitors of aromatase. In the sub-series of 3-(azolylmethyl)-1H-indoles, four imidazole derivatives and their triazole analogues were tested. Imidazole derivatives 11 and 14 in which the benzyl moiety was substituted by 2-chloro and 4-cyano groups, respectively, were the most active, with IC50 values ranging between 0.054 and 0.050 μM. In the other sub-series, eight 3-(α-azolylbenzyl)-1H-indoles were prepared and tested. Compound 30, the N-ethyl imidazole derivative, proved to be an aromatase inhibitor, showing an IC50 value of 0.052 μM. All target compounds were further evaluated against 17α-hydroxylase/C17,20-lyase to determine their selectivity profile. 相似文献
4.
Belma Zengin Kurt Busecan Aksoydan Ramin Ekhteiari Salmas Andrea Angeli 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):1042-1052
New coumaryl-carboxamide derivatives with the thiourea moiety as a linker between the alkyl chains and/or the heterocycle nucleus were synthesized and their inhibitory activity against the human carbonic anhydrase (hCA) isoforms hCA I, II, VII and IX were evaluated. While the hCA I, II and VII isoforms were not inhibited by the investigated compounds, the tumour-associated isoform hCA IX was inhibited in the high nanomolar range. 2-Oxo-N-((2-(pyrrolidin-1-yl)ethyl)carbamothioyl)-2H-chromene-3-carboxamide (e11) exhibited a selective inhibitory action against hCA IX with the Ki of 107.9?nM. In order to better understand the inhibitory profiles of studied molecules, multiscale molecular modeling approaches were used. Different molecular docking algorithms were used to investigate binding poses and predicted binding energies of studied compounds at the active sites of the CA I, II, VII and IX isoforms. 相似文献
5.
Summary A variety of 2-arylthio-N-alkylmaleimides were prepared, and their antimicrobial activities were examined. Almost all of these compounds exhibited antibacterial activity against Gram-positive bacteria such asBacillus subtilis andStaphylococcus aureus. Some compounds such as 2-(halogeno-phenyl)-thio-N-methylmaleimides (4, 5, 6, 8 and 10) and 2-(2-carbamoylphenyl)thio-N-methylmaleimide(35) exhibited antibacterial activity againstEscherichia coli. All compounds tested were inactive againstPseudomonas aeruginosa except 2-(2-carbamoylphenyl)thio-N-methylmaleimide(35) which was marginally active. Activities against Gram-positive bacteria were not due to the effect of the substituent on the benzene ring, except in the instances 2-carboxy, 2-carbomethoxy, 2-amino groups and alkyl chains, however, activities against Gram-negative bacteria were due to phenylthio and the alkyl substituents. Some of 2-arylthio-N-alkylmaleimides were examined for their antifungal activities using eight strains of fungi, and they showed activity against these. 相似文献
6.
Antibacterial activity of quaternary ammonium chitosan containing mono or disaccharide moieties: Preparation and characterization 总被引:1,自引:0,他引:1
Warayuth Sajomsang Pattarapond Gonil Supawan Tantayanon 《International journal of biological macromolecules》2009,44(5):419-427
The 9 quaternary ammonium chitosans containing monosaccharides or disaccharides moieties were successfully synthesized by reductive N-alkylation then quaternized by N-(3-chloro-2-hydroxypropyl) trimethylammonium chloride (Quat-188). The chemical structures of quaternary ammonium chitosan derivatives were characterized by ATR-FTIR and 1H NMR spectroscopy. The degree of N-substitution (DS) and the degree of quaternization (DQ) were determined by 1H NMR spectroscopic method. It was found that the DS was in the range of 12–40% while the DQ was in the range of 90–97%. The results indicated that the O-alkylation was occured in this condition. Moreover, all quaternary ammonium chitosan derivatives were highly water-soluble at acidic, basic, and neutral pH. Minimum inhibitory concentration (MIC) antibacterial studies of these materials were carried out on Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria compared to quaternary ammonium N-octyl and N-benzyl chitosan derivatives. The quaternary ammonium mono and disaccharide chitosan derivatives showed very high MIC values which were in the range of 32 to >256 μg/mL against both bacteria. Also it was found that the antibacterial activity decreased with increasing the DS. This was due to the increased hydrophilicity of mono and disaccharide moieties. On the other hand, the low MIC values (8–32 μg/mL) were obviously observed when the DS of quaternary ammonium N-octyl and N-benzyl chitosan derivatives was lower than 18%. The results showed that the presence of hydrophobic moiety such as the N-benzyl group enhanced the antibacterial activity compared to the hydrophilic moiety against both bacteria. 相似文献
7.
Mange R. Yadav Anil K. Shinde Bishram S. Chouhan Rajani Giridhar Robert Menard 《Journal of enzyme inhibition and medicinal chemistry》2013,28(2):190-197
Cathepsins have been found to have important physiological roles. The implication of cathepsin L in various types of cancers is well established. In a search for selective cathepsin L inhibitors as anticancer agents, a series of 2-cyanoprrolidine peptidomimetics, carrying a nitrile group as warhead, were designed. Two series of compounds, one with a benzyl moiety and a second with an isobutyl moiety at P2 position of the enzyme were synthesized. The synthesized compounds were evaluated for inhibitory activity against human cathepsin L and cathepsin B. Although, none of the compounds showed promising inhibitory activity, (E)N-{(S)1-[(S)2-cyano-1-pyrrolidinecarbonyl]-3-methylbutyl}-2,3-diphenylacrylamide (24) with an isobutyl moiety at P2 was found to show selectivity as a cathepsin L inhibitor (Ki 5.3 μM for cathepsin L and Ki > 100 μM for cathepsin B). This compound could act as a new lead for the further development of improved inhibitors within this inhibitor type. 相似文献
8.
Mohammad Shaharyar Mohamed Ashraf Ali Mohammad Afroz Bakht Vel Murugan 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):432-436
Compounds based on the isoxazoline moiety were screened for their antimycobacterial activity in vitro against Mycobacterium tuberculosis H37R (MTB), and INH (isoniazid) resistant Mycobacterium tuberculosis (INHR-MTB) using the agar dilution method and bactec 460. Among the synthesized compounds, 4-[5-(4-bromophenyl)-4,5-dihydro-3-isoxazolyl]-2-methylphenol (4l) was found to be the most active agent against MTB and INHR-MTB with minimum inhibitory concentration of 0.62 μM. When compared to INH, compound (4l) was 1.12 fold and 3.0 fold more active against MTB and INHR-MTB, respectively. 相似文献
9.
Andrea Scozzafava Bogdan Iorga 《Journal of enzyme inhibition and medicinal chemistry》2013,28(2):139-161
Reaction of histamine (Hst) with tetrabromophthalic anhydride and protection of its imidazole moiety with tritylsulfenyl chloride, followed by hydrazinolysis, afforded N-1-tritylsulfenyl histamine, a key intermediate which was further derivatized at its aminoethyl moiety. Reaction of the key intermediate with 4-tosylureido amino acids/dipeptides (ts-AA) in the presence of car-bodiimides, afforded after deprotection of the imidazole moiety, a series of compounds with the general formula ts-AA-Hst (ts = 4-MeC6H4SO2NHCO). Some structurally related dipeptide derivatives with the general formula ts-AA l-AA2-Hst, were also prepared, by in a similar way to the amino acyl compounds mentioned above. The new derivatives were examined as activators of three carbonic anhydrase (CA) isozymes, hCA I, hCA II (cytosolic forms) and bCA IV (membrane-bound form). Efficient activation was observed against all three isozymes, but especially against hCA I and bCA IV, with affinities in the 1-10 nanomolar range for the best compounds. hCA II was on the other hand activatable with affinities around 20-50 nM. This new class of CA activators might lead to the development of drugs/diagnostic agents for the CA deficiency syndrome, a genetic disease of bone, brain and kidneys. 相似文献
10.
《Bioscience, biotechnology, and biochemistry》2013,77(9):1448-1450
New derivatives of pyridinyloxyphenoxypropionamide were synthesized, which have an unnatural α-amino acid or its decarboxylated structure as amide moieties. Some compounds such as N-(1-metboxycarbonyl-l-tert-butylamino)methyl, N-methoxymethyl and N-hydroxymethyl 2-[4-(3-chloro-5-trifluoromethyl-2-pyridinyloxy)phenoxy] propionamide were found to show stronger herbicidal activity against grass weeds than that of pyridinyloxyphenoxypropionamides which have already been synthesized. 相似文献
11.
Koichi Yoneyama Nobumasa Ichizen Makoto Konnai Tetsuo Takematsu Kazuyuki Ushinohama Tetsuo Jikihara 《Bioscience, biotechnology, and biochemistry》2013,77(11):3265-3269
N-Acyl- and N-sulfonyl-N-(2,3-epoxypropyl)benzenesulfonamide derivatives were synthesized and their herbicidal activities were tested against barnyardgrass and rice plants by the pot and the petri dish tests in order to examine the structural requirements for herbicidal activity in N-(2,3-epoxypropyl)benzenesulfonamide derivatives. The N-sulfonylbenzenesulfonamide derivatives exhibited higher activity against barnyardgrass than the N-acylbenzenesulfonamide derivatives, and were found to be as active as N-(2,3-epoxypropyl)-N-(α-methylbenzyl)benzenesulfonamide. Some of the N-sulfonylbenzenesulfonamide derivatives showed high selectivity towards barnyardgrass and rice plants at their germination stage. 相似文献
12.
A new class of 2-aryloxy-N-phenylacetamide and N′-(2-aryloxyoxyacetyl) benzohydrazide derivatives with different active moieties were synthesized and screened for their antibacterial activity. Structural characterization of synthesized compounds was performed using HR-MS, 1H-NMR, and 13C-NMR spectral data. Amongst the synthesized compounds, 4-{2-[2-(2-chloroacetamido)phenoxy]acetamido}-3-nitrobenzoic acid ( 3h ) and 2-chloro-N-(2-{2-[2-(2-chlorobenzoyl)hydrazinyl]-2-oxoethoxy}phenyl)acetamide ( 3o ) have shown good antibacterial activity against a selected panel of bacteria. Besides, compounds also exhibited bactericidal activity against P. aeruginosa ( 3h , 0.69 μg/mL) and S. aureus ( 3o , 0.62 μg/mL) as evident by MBC and time-kill kinetics studies. In silico molecular docking and ADMET properties of newly synthesized compounds revealed that compounds could be considered as promising antibacterial agents. 相似文献
13.
Ahmed G. Eissa James A. Blaxland Rhodri O. Williams Kamel A. Metwally Sobhy M. El-Adl El-Sayed M. Lashine 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):1694-1697
The synthesis of a series of benzimidazole-N-benzylpropan-1-amines and adenine-N-benzylpropan-1-amines is described. Subsequent evaluation against two strains of the anaerobic bacterium Clostridium difficile was performed with three amine derivatives displaying MIC values of 16?μg/mL. Molecular docking studies of the described amines determined that the amines interact within two active site pockets of C. difficile methionyl tRNA synthetase with methoxy substituents in the benzyl ring and an adenine biaryl moiety resulting in optimal binding interactions. 相似文献
14.
TLCK (N-α-tosyl-L-lysine chloromethyl ketone) inhibits protein kinase C whether or not the enzyme is under the regulation of Ca2+ and phospholipid. TLCK (IC50= 1 mM) is a much more potent inhibitor of protein kinase C than TPCK (N-α-tosyl-L-phenylalanine chloromethyl ketone) (IC50=8 mM), suggesting that the lysyl moiety of TLCK may be specifically recognized by the active site of protein kinase C. These results extend the evidence that the active site of protein kinase C recognizes basic amino acids, and suggest that the active sites of protein kinase C and the cAMP-dependent protein kinase, which is also inhibited by TLCK and TPCK, are structurally related.Protein kinase CTumor promotionProtease inhibitor 相似文献
15.
Delia Preti Riccardo Rondanin Barbara Cacciari Ernest Hamel Jan Balzarini 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):1225-1238
Inhibition of microtubule function using tubulin targeting agents has received growing attention in the last several decades. The indole scaffold has been recognized as an important scaffold in the design of novel compounds acting as antimitotic agents. Indole-based chalcones, in which one of the aryl rings was replaced by an indole, have been explored in the last few years for their anticancer potential in different cancer cell lines. Eighteen novel (3′,4′,5′-trimethoxyphenyl)-indolyl-propenone derivatives with general structure 9 were synthesized and evaluated for their antiproliferative activity against a panel of four different human cancer cell lines. The highest IC50 values were obtained against the human promyelocytic leukemia HL-60 cell line. This series of chalcone derivatives was characterized by the presence of a 2-alkoxycarbonyl indole ring as the second aryl system attached at the carbonyl of the 3-position of the 1-(3′,4′,5′-trimethoxyphenyl)-2-propen-1-one framework. The structure–activity relationship (SAR) of the indole-based chalcone derivatives was investigated by varying the position of the methoxy group, by the introduction of different substituents (hydrogen, methyl, ethyl or benzyl) at the N-1 position and by the activity differences between methoxycarbonyl and ethoxycarbonyl moieties at the 2-position of the indole nucleus. The antiproliferative activity data of the novel synthesized compounds revealed that generally N-substituted indole analogues exhibited considerably reduced potency as compared with their parent N-unsubstituted counterparts, demonstrating that the presence of a hydrogen on the indole nitrogen plays a decisive role in increasing antiproliferative activity. The results also revealed that the position of the methoxy group on the indole ring is a critical determinant of biological activity. Among the synthesized derivatives, compound 9e, containing the 2-methoxycarbonyl-6-methoxy-N-1H-indole moiety exhibited the highest antiproliferative activity, with IC50 values of 0.37, 0.16 and 0.17?μM against HeLa, HT29 and MCF-7 cancer cell lines, respectively, and with considerably lower activity against HL-60 cells (IC50: 18?μM). This derivative also displayed cytotoxic properties (IC50 values ~1?μM) in the human myeloid leukemia U-937 cell line overexpressing human Bcl-2 (U-937/Bcl-2) via cell cycle progression arrest at the G2-M phase and induction of apoptosis. The results obtained also demonstrated that the antiproliferative activity of this molecule is related to inhibition of tubulin polymerisation. The presence of a methoxy group at the C5- or C6-position of the indole nucleus, as well as the absence of substituents at the N-1-indole position, contributed to the optimal activity of the indole-propenone-3′,4′,5′-trimethoxyphenyl scaffold. 相似文献
16.
Rui Yang Zhuolin Li Jialing Xie Jianchuan Liu Tianhong Qin Junda Liu Haiying Du Haoyun Ye 《化学与生物多样性》2021,18(5):e2100106
In search of new environmentally friendly and effective antifungal agents, a series of 4-aminoquinolines bearing a 1,3-benzodioxole moiety were prepared and their structures were fully elucidated by spectroscopic analyses. The antifungal activities of all the target compounds against five phytopathogenic fungi were evaluated in vitro. The results revealed that most of the newly synthesized compounds exhibited obvious inhibitory activities at the concentration of 50 μg/mL. Among them, 6-(furan-2-yl)-N-(4-methylphenyl)-2H-[1,3]dioxolo[4,5-g]quinolin-8-amine hydrochloride ( 7m ) displayed more promising antifungal potency with EC50 values of 10.3 and 14.0 μg/mL against C. lunata and A. alternate, respectively. Particularly, the EC50 value of 7m against C. lunata was 7.3-fold as potent as the standard azoxystrobin. There were some significant morphological alterations in the mycelia of C. lunata when treated with 7m at 50 μg/mL. Additionally, the preliminary structure–activity relationships (SARs) were also discussed. Thus, this study suggests that 4-aminoquinolines bearing a 1,3-benzodioxole moiety are interesting scaffolds for the development of novel antifungal agents. 相似文献
17.
Yoshimitsu Yamazaki Hidekatsu Maeda 《Bioscience, biotechnology, and biochemistry》2013,77(9):2091-2103
Three polymerizable ATP derivatives, N6-[N-(6-methacrylamidohexyl)carbamoylmethyl]-, N6-[N -[2-[N -(2-methacrylamidoethyl)carbamoyl]ethyl]carbamoylmethyl]-, and N6 -[N -[N -(2-hydroxy- 3-methacrylamidopropyl)carbamoylmethyl]carbamoylmethyl]-ATP, were synthesized and radically copolymerized with comonomers [acrylamide, N -(2-hydroxyethyl)-, N -ethyl-, N, N - diethylacrylamide, acrylic acid, and 6-methacrylamidohexylammonium chloride] to obtain 18 new polymer derivatives of ATP. The molecular weight distributions were controlled by appropriate initiator concentrations. The monomeric and polymeric ATP derivatives were all coenzymically active against both hexokinase and glycerol kinase. The observed coenzymic activities (Km and Vmax) are discussed in connection with the structures of the derivatives. 相似文献
18.
Yuji Sumita Michiyo Shirato Yoshihito Ueno Akira Matsuda Satoshi Shuto 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):175-187
Abstract The synthesis of cyclic ADP-carbocyclic-ribose (2), as a stable mimic for cyclic ADP-ribose, was investigated. Construction of the 18-membered backbone structure was successfully achieved by condensation of the two phosphate groups of 19, possibly due to restriction of the conformation of the substrate in a syn-form using an 8-chloro substituent at the adenine moiety. SN2 reactions between an optically active carbocyclic unit 8, which was constructed by a previously developed method, and 8-bromo-N 6-trichloroacetyl-2′,3′-O-isopropylideneadenosine 9c gave N-1-carbocyclic derivative, which was deprotected to give 5′,5′-diol derivatives 18. When 18 was treated with POCl3 in PO(OEt)3, the bromo group at the 8-position was replaced to give N-1-carbocyclic-8-chloroadenosine 5′,5′-diphosphate derivative 19 in 43% yield. Treatment of 19 with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride gave the desired intramolecular condensation product 20 in 10% yield. This is the first chemical construction of the 18-membered backbone structure containing an intramolecular pyrophosphate linkage of a cADPR-related compound with an adenine base. 相似文献
19.
Sh. H. Abdel-Hafez 《Russian Journal of Bioorganic Chemistry》2010,36(3):370-376
Synthesis of 3-[4-(N-substituted sulfamoyl)phenyl]-3,4-dihydro-4-oxo-7,9-dimethylpyri-do[3′,2′:4,5]selenolo[3,2-d]pyrimidines,7-[4-(N-substituted sulfamoyl)phenyl]-7,8-dihydro-8-oxo-3,4-diphenylpyrimido[4′,5′:4,5]selenolo [2,3-c]pyridazines and 1-[4-(N-substituted sulfamoyl)phenyl]-1,11-dihydro 11-oxo-4-methylpyrimido[4′,5′:4,5]selenolo[2,3-b]quinolines is reported. 4-Amino-N-pyrimidine-2-ylbenzene sulfonamide (a), 4-amino-N-(2,6-dimethylpyrimidin-4-yl)benzene sulfonamide (b), N-[(4-aminophenyl)sulfonyl] acetamide (c) with N-ethoxymethyleneamino of selenolo pyridine, selenolo pyridazine and selenolo quinoline derivatives respectively were obtained
starting from 1-amino-N
4-substituted sulfanilamides. Spectroscopic data (IR, 1H NMR, 13C NMR and Mass spectral) confirmed the structure of the newly synthesized compounds. Substituted
pyrimidines, pyridazines and quinolines were screened for antibacterial activity against gram-positive and gram-negative bacteria. Selenolo derivative of N-[(4-aminophenyl)sulfonyl] acetamide (substitutent of sulfacetamide c) showed strong bactericidal effect against all the tested
organisms. Selenolo[3,2-d]pyrimidin (substitutent a) showed a good bactericidal effect against Serratia marcescens, Staphylococcus aureus and Escherichia coli. Compounds selenolo[2,3-c]pyridazine (substitutent b), selenolo[2,3-b]quinoline(substitutents c)) exhibited a moderate bactericidal effect against Serratia marcescens. None of the synthesized seleno pyridazines has a considerable antimicrobial activity against the tested organisms. The minimum
inhibitory concentration (MIC) of the most active compound-3-[4-(N-acetyl sulfamoyl)phenyl]-3,4-dihydro-4-oxo-7,9-dimethylpyrido[3′,2′:4,5]selenolo [3,2-d]pyrimidine was 10 mg ml−1. 相似文献
20.
Claudiu T. Supuran Fabrizio Briganti Giovanna Mincione Andrea Scozzafava 《Journal of enzyme inhibition and medicinal chemistry》2013,28(2):111-128
L-alanine hydroxamate derivatives were obtained by reaction of alkyl/arylsulfonyl halides with L-alanine, followed by treatment with benzyl chloride, and conversion of the COOH moiety to the CONHOH group with hydroxylamine in the presence of carbodiimides. Other derivatives were obtained by reaction of N-benzyl-alanine with aryl isocyanates, arylsulfonyl isocyanates or benzoyl isothiocyanate, followed by a similar conversion of the COOH to the CONHOH moiety. The obtained compounds were assayed as inhibitors of Clostridium histolyticum collage-nase, ChC (EC 3.4.24.3), a zinc enzyme which degrades triple helical collagen. The hydroxamate derivatives were generally 100-500 times more active than the corresponding carboxylates. In the series of synthesized derivatives, substitution patterns leading to the most potent ChC inhibitors were those involving perfluoroalkylsulfonyl-and substituted-arylsulfonyl moieties, such as pentafluorophenylsulfonyl, 3- and 4-protected-aminophenylsulfonyl-, 3- and 4-carboxy-phenylsulfonyl-, 3-trifluoromethyl-phenylsulfonyl-, or 1- and 2-naphthylsulfonyl among others. Similarly to the matrix metalloproteinase (MMP) hydroxamate inhibitors, ChC inhibitors of the type reported here must incorporate hydrophobic moieties at the P2, and P3 sites, in order to achieve tight binding to the enzyme. 相似文献