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1.
Yan Lu Zhao Wang Chien-Ming Li Jianjun Chen James T. Dalton Wei Li Duane D. Miller 《Bioorganic & medicinal chemistry》2010,18(2):477-495
A series of (2RS,4R)-2-arylthiazolidine-4-carboxylic acid amide (ATCAA) was synthesized. Antiproliferative activity against melanoma and prostate cancer cells compared with control cells (fibroblast and RH7777, respectively) was evaluated. Compound 3id showed the best selectivity and growth-inhibition activity against three melanoma cell lines (B16-F1, A375, and WM-164). Compounds 15b and 3ac had good selectivity and potency against four prostate cancer cell lines (DU 145, PC-3, LNCaP, and PPC-1). The structure–activity relationship (SAR) of the side chain, the thiazolidine ring, and phenyl substituents is discussed. Cell cycle analysis showed that the percentage of cancer cells undergoing apoptosis (sub-G1 phase) increased after treatment with 1b and 3ad, which also strongly inhibited melanoma colony formation. In vivo studies on nude mice bearing A375 melanoma tumors showed that compound 1b inhibited tumor growth in a dose-dependent manner. At a dose of 10 mg/kg, 1b significantly inhibited melanoma tumor growth and showed higher efficacy than did dacarbazine at 60 mg/kg. 相似文献
2.
Simon Ingate Ana San-Félix Erik De Clercq Jan Balzarini Maríia-José Camarasa 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):299-301
Abstract Derivatives of TSAO-T based upon pentofuranose sugars with the L-configuration have been prepared and evaluated as inhibitors of HIV-1 induced cytopathicity. 相似文献
3.
Akira Hasegawa Masahiko Ozaki Yasuhiko Goh Makoto Kiso Ichiro Azuma 《Carbohydrate research》1982,100(1):235-245
Benzoylation of benzyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-α-d-glucopyranoside, benzyl 2-deoxy-2-(dl-3-hydroxytetradecanoylamino)-4,6-O-isopropylidene-α-d-glucopyranoside, and benzyl 2-deoxy-4,6-O-isopropylidene-2-octadecanoylamino-β-d-glucopyranoside, with subsequent hydrolysis of the 4,6-O-isopropylidene group, gave the corresponding 3-O-benzoyl derivatives (4, 5, and 7). Hydrogenation of benzyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-α-d-glucopyranoside, followed by chlorination, gave a product that was treated with mercuric actate to yield 2-acetamido-1,4,6-tri-O-acetyl-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-β-d-glucopyranose (11). Treatment of 11 with ferric chloride afforded the oxazoline derivative, which was condensed with 4, 5, and 7 to give the (1→6)-β-linked disaccharide derivatives 13, 15, and 17. Hydrolysis of the methyl ester group in the compounds derived from 13, 15, and 17 by 4-O-acetylation gave the corresponding free acids, which were coupled with l-alanyl-d-isoglutamine benzyl ester, to yield the dipeptide derivatives 19–21 in excellent yields. Hydrolysis of 19–21, followed by hydrogenation, gave the respective O-(N-acetyl-β-muramoyl-l-alanyl-d-isoglutamine)-(1→6)-2-acylamino-2-deoxy-d-glucoses in good yields. The immunoadjuvant activity of these compounds was examined in guinea-pigs. 相似文献
4.
Sunny Manohar Shabana I. Khan Diwan S. Rawat 《Bioorganic & medicinal chemistry letters》2010,20(1):322-325
A series of 4-aminoquinoline–triazine conjugates with different substitution pattern have been synthesized and evaluated for their in vitro antimalarial activity against chloroquine-sensitive and resistant strains of Plasmodium falciparum. Compounds 16, 19, 28 and 35 exhibited promising antimalarial activity against both strains of P. falciparum. Cytotoxicity of these compounds was tested against three cell lines. Several compounds did not show any cytotoxicity up to a high concentration (48 μM), others exhibited mild toxicities but selective index for antimalarial activity was high for most of these conjugates. 相似文献
5.
Summary In search for more potent, particularly less ulcerogenic gastritis that hopefully replace the universal NSAID Diclofenac, (2-[(2,6-di-chlorophenyl)amino]-phenylacetic acid, C.A.S. 15307-86-5), twelve new non-proteinogenic amino acid conjugates of the drug, namely that of sarcosine,-alanine, D-leucine and D-phenylalanine, were synthesized and biologically screened for their anti-inflammatory, analgesic and ulcerogenic activity in rats.Diclofenac amino acid esters (IIa-d), were synthesizedvia the corresponding HOSu or HOBt active esters. Alkaline hydrolysis (NaOH) followed by acidification (KHSO4) or thioamide formation (Lawsson's Reagent, C.A.S. 19172-47-5), afforded the corresponding free acids IIIa-d or the thioamides IVa-d respectively.Interestingly, in contrary to the parent Diclofenac, the synthesized candidates (except IIId), were entirly nonulcerogenic in rats. Further, they considerably retained a generelized anti-phlogistic activity. The major Diclofenac irritating gastric side effect was thus eliminated.Particularly, the sarcosine conjugate IIa and its thiomimic IVa exhibit promising therapeutic perspectives.Preliminary results were presented and discussed at the 5th International Congress on Amino Acids, August 25–29, 1997, Chalkidiki, Greece and abstracted in Amino Acids (1997) 15/1: 75. 相似文献
6.
Cociorva OM Li B Nomanbhoy T Li Q Nakamura A Nakamura K Nomura M Okada K Seto S Yumoto K Liyanage M Zhang MC Aban A Leen B Szardenings AK Rosenblum JS Kozarich JW Kohno Y Shreder KR 《Bioorganic & medicinal chemistry letters》2011,21(19):5948-5951
The synthesis, GSK-3β inhibitory activity, and anti-microbial activity of bicyclic and tricyclic derivatives of the 5,7-diamino-6-fluoro-4-quinolone-3-carboxylic acid scaffold were studied. Kinase selectivity profiling indicated that members of this class were potent and highly selective GSK-3 inhibitors. 相似文献
7.
《Bioorganic & medicinal chemistry》2014,22(13):3449-3454
2-Arylquinazolin-4(3H)-ones 1–25 were synthesized by reacting anthranilamide with various benzaldehydes using CuCl2·2H2O as a catalyst in ethanol under reflux. Synthetic 2-arylquinazolin-4(3H)-ones 1–25 were evaluated for their β-glucuronidase inhibitory potential. A trend of inhibition IC50 against the enzyme in the range of 0.6–198.2 μM, was observed and compared with the standard d-saccharic acid 1,4-lactone (IC50 = 45.75 ± 2.16 μM). Compounds 13, 19, 4, 12, 14, 22, 23, 25, 15, 8, 17, 11, 21, 1, 3, 18, 9, 2, and 24 with the IC50 values within the range of 0.6–44.0 μM, indicated that the compounds have superior activity than the standard. The compounds showed no cytotoxic effects against PC-3 cells. A structure–activity relationship is established. 相似文献
8.
The optimum geometries and binding energies of the complexes formed by AMPA and Kainic acid, as well as their anions with
tyrosine, proline and some tripeptides are investigated with quantum chemical calculations (HF/6-31G**). It was found that
receptors featuring the Tyr-Ala-Pro sequence exhibit stronger binding energies to the substrates than the Tyr-Ser-Pro and
Tyr-Ser-Ser. As expected, the anions are more bound than the neutral species. This work can lead to investigations on the
effect of AMPA receptors mutations on the brain functions, possibly related to criminal tendencies. 相似文献
9.
Chiara Rusconi Nadia Vaiana Manolo Casagrande Nicoletta Basilico Silvia Parapini Donatella Taramelli Sergio Romeo Anna Sparatore 《Bioorganic & medicinal chemistry》2012,20(19):5980-5985
Recently the N-(?)-lupinyl-derivative of 7-chloro-4-aminoquinoline ((?)-AM-1; 7-chloro-4-{N-[(1S,9aR)(octahydro-2H-quinolizin-1-yl)methyl]amino}quinoline) showed potent in vitro and in vivo activity against both Chloroquine susceptible and resistant strains of Plasmodium falciparum. However, (?)-AM-1 is synthesized starting from (?)-lupinine, an expensive alkaloid isolated from Lupinus luteus whose worldwide production is not sufficient, at present, for large market purposes. To overcome this issue, the corresponding racemic compound, derived from synthetic (±)-lupinine was considered a cheaper alternative for the development of a novel antimalarial agent. Therefore, the racemic and the 7-chloro-4-(N-(+)-lupinyl)aminoquinoline ((±)-AM-1; (+)-AM-1) were synthesized and their in vitro antimalarial activity and cytotoxicity compared with those of (?)-AM-1. The (+)-lupinine required for the synthesis of (+)-AM-1 was obtained through a not previously described lipase catalyzed kinetic resolution of (±)-lupinine. In terms of antimalarial activity, (±)-AM1 and (+)-AM1 demonstrated very good activity in vitro against both CQ-R and CQ-S strains of P. falciparum (range IC50 16–35 nM), and low toxicity against human normal cell lines (therapeutic index >1000), comparable with that of (?)-AM1. These results confirm that the racemate (±)-AM1 could be considered as a potential antimalarial agent, ensuring a decrease of costs of synthesis compared to (?)-AM1. 相似文献
10.
Anand R. Saundane Katkar Vijaykumar A. Verma Vaijinath 《Bioorganic & medicinal chemistry letters》2013,23(7):1978-1984
As a part of systematic investigation of synthesis and biological activities of indole analogues linked to various heterocyclic systems, we have synthesized new compounds viz., 2-amino-4-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-4H-pyran-3-carbonitriles (2a–i), 4,5-diamino-6-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-8-aryl-2-oxo-2,6-dihydrodipyrano [2,3-b:3,2-e]pyridine-3-carbonitriles (3a–i), 4-amino-5-(5′-substituted 2′-phenyl-1H-indol-3-yl)-7-aryl-1H-pyrano[2,3-d]pyrimidin-2(5H)-ones (4a–i), 4-amino-5-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-7-aryl-1H-pyrano[2,3-d]pyrimidin-2(5H)-thiones (5a–i), 4-(5′-subtituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-1,4-dihydropyrano[2,3-c]pyrazol-3-amines (6a–i) and 5-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-7-aryl-3H-pyrano[2,3-d]pyrimidin-4(5H)-ones (7a–i). Antibacterial activity results revealed that, compound 6a showed promising activity versus Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. Compound 6d exhibited good activity against S. aureus, K. pneumoniae and Pseudomonas aeruginosa. Antifungal activity results indicated that, compound 4d exhibited maximum zone of inhibition against Aspergillus oryzae and Aspergillus flavus. In case of antioxidant activity, compound 4a showed promising radical scavenging activity, ferric ions (Fe3+) reducing antioxidant power (FRAP) and metal chelating activity. 相似文献
11.
J. Du J. J. Duan Q. Zhang J. Hou F. Bai N. Chen G. Bai 《Applied Biochemistry and Microbiology》2012,48(2):159-166
L-Tryptophan (L-Trp) is an essential amino acid. It is widely used in medical, health and food products, so a low-cost supply
is needed. There are 4 methods for L-Trp production: chemical synthesis, extraction, enzymatic synthesis, and fermentation.
In this study, we produced a recombinant bacterial strain pET-tnaA of Escherichia coli which has the L-tryptophanase gene. Using the pET-tnaA E. coli and the strain TS1138 of Pseudomonas sp., a one-pot enzymatic synthesis of L-Trp was developed. Pseudomonas sp. TS1138 was added to a solution of D,L-2-amino-Δ2-thiazoline-4-carboxylic acid (DL-ATC) to convert it to L-cysteine (L-Cys).
After concentration, E. coli BL21 (DE 3) cells including plasmid pET-tnaA, indole, and pyridoxal 5’-phosphate were added. At the optimum conditions, the
conversion rates of DL-ATC and L-Cys were 95.4% and 92.1%, respectively. After purifying using macroporous resin S8 and NKA-II,
10.32 g of L-Trp of 98.3% purity was obtained. This study established methods for one-pot enzymatic synthesis and separation
of L-Trp. This method of producing L-Trp is more environmentally sound than methods using chemical synthesis, and it lays
the foundations for industrial production of L-Trp from dl-ATC and indole. 相似文献
12.
The 13C.n.m.r spectra of water-soluble and -insoluble glucans synthesized by enzymes isolated from six strains of Streptococcus mutans are interpreted. The glucans are shown to be composed primarily of α(1→3)- and α-(1→6)-linked glucosyl residues, and the relative abundance of each linkage is estimated from peak areas. Treatment of water-insoluble glucans with dextranase is found to result in water-soluble and -insoluble products, the former enriched in α-(1→6)-linkages and the latter in α-(1→3)-linkages. The structural conclusions arrived at by 13C-n.m.r. spectroscopy are consistent with data from methylation analysis and 1H-n.m.r. spectroscopy. 相似文献
13.
Barbosa VA Formagio AS Savariz FC Foglio MA Spindola HM de Carvalho JE Meyer E Sarragiotto MH 《Bioorganic & medicinal chemistry》2011,19(21):6400-6408
A series of β-carboline derivatives bearing a substituted-carbohydrazide moiety at C-3 were synthesized and evaluated for their antitumor activity against eight human cancer cell lines. The β-carboline N-(substituted-benzylidene)carbohydrazides showed, in general, a greater antitumor activity than their N-(alkylidene)carbohydrazide analogues. The N(9)-methylation of β-carboline N-(substituted-benzylidene) carbohydrazides resulted in a decrease of antitumor activity. Among compounds tested, the benzylidene-carbohydrazides 3, 4, 11, 13, 16, 21 and 22 were the most active, possessing IC(50) less than 10 μM for six of the eight tumor cell lines assayed. The derivative 4 displayed the most significant activity toward all tested cell lines, with a remarkable cytotoxicity against renal (786-0) cell lines (IC(50)=0.04 μM). Compound 4 was assayed for its in vivo antineoplastic activity in the Ehrlich solid carcinoma assay. 相似文献
14.
Structure–activity relationship of indoline-2-carboxylic acid N-(substituted)phenylamide derivatives
Jae-Hwan Kwak Yoseob Kim Hyunjeong Park Jae-Yong Jang Keun Kuk Lee Wonhui Yi Jeong-Ah Kwak Song-Gyu Park Hwanmook Kim Kiho Lee Jong Soon Kang Sang-Bae Han Bang Yeon Hwang Jin Tae Hong Jae-Kyung Jung Youngsoo Kim Jungsook Cho Heesoon Lee 《Bioorganic & medicinal chemistry letters》2010,20(15):4620-4623
Chroman derivatives exhibited potent inhibitory activity of NF-κB. For SAR, the chroman scaffold was modified with an indoline moiety. A series of indoline-2-carboxylic acid N-(substituted)phenylamide derivatives were synthesized to explore their inhibitory activities of NF-κB and they were also evaluated for cytotoxicity against various cancer cell lines. Since intermediates with Boc showed outstanding results, various substituents in place of the Boc group were introduced additionally and these compounds were also evaluated for SAR. 相似文献
15.
《Journal of Molecular Catalysis .B, Enzymatic》1998,4(4):219-227
Racemic (1SR,2SR,4SR,5SR)-2-[(4′-hydroxy-3′-methoxy)-phenoxy]-4-(4″-hydroxy-3″-methoxy-phenyl)-8-hydroxy-6-oxo-3-oxabicyclo[3.3.0]-7-octene (2, C21H20O8) was isolated as major product of soybean lipoxygenase action on curcumin (1, C21H20O6). The structure of 2 was elucidated by HPLC-APCI-MS and tandem MS, 1H, 13C, DEPT, H,H-COSY, H,C-HMQC, H,C-HMBC and phase sensitive 2D NOESY NMR techniques. For kinetic studies the rate of substrate degradation was followed spectrophotometrically at 430 nm, and the rate of oxygen consumption was measured polarographically. As evaluated by both methods, Km for 1 was about four times higher than that obtained for linoleic acid (as the best substrate for soybean lipoxygenase); Vmax was reduced five-fold. Lipoxygenase-mediated oxygenation of 1 was confirmed by the following criteria: (i) curcumin did not react with inactivated lipoxygenase; (ii) the enzymatic reaction was strongly inhibited by inhibitors such as BHA, deferoxamine and HgCl2; (iii) oxygen consumption (measured polarographically) and curcumin degradation (measured photometrically) were shown to occur simultaneously at a ratio of 0.8 to 1, suggesting insertion of oxygen into 1 by lipoxygenase; (iv) molecular mass estimation by APCI-MS showed a shift of 32 in molecular mass from 1 (Mr 368) to 2 (Mr 400) being equivalent to an insertion of dioxygen. Curcumin meets none of the common features for lipoxygenase substrates and, therefore, may represent a new type of substrates for this enzyme. 相似文献
16.
Faten Sliman Mélina Blairvacq Emilie Durieu Laurent Meijer Jordi Rodrigo Didier Desmaële 《Bioorganic & medicinal chemistry letters》2010,20(9):2801-2805
Pim-1 kinase is a cytoplasmic serine/threonine kinase that controls programmed cell death by phosphorylating substrates that regulate both apotosis and cellular metabolism. A series of 2-styrylquinolines and quinoline-2-carboxamides has been identified as potent inhibitors of the Pim-1 kinase. The 8-hydroxy-quinoline 7-carboxylic acid moiety appeared to be a crucial pharmacophore for activity. Molecular modeling indicated that interaction of this scaffold with Asp186 and Lys67 residues within the ATP-binding pocket might be responsible for the kinase inhibitory potency. 相似文献
17.
Zhi-Hao Shi Nian-Guang Li Qian-Ping Shi Hao Tang Yu-Ping Tang Wei Li Lian Yin Jian-Ping Yang Jin-Ao Duan 《Bioorganic & medicinal chemistry letters》2013,23(5):1206-1211
Four series of acid amides were synthesized, and through measurement using a fluorogenic substrate assay with human recombinant MMP-1, MMP-2 and MMP-9, compound 3f showed considerable inhibitory activities against MMP-2, MMP-9 and the best selectivity over MMP-1. Preliminary structure–activity relationship analysis indicated that caffeic acid amides with electron-donating groups at para-position of amino phenyl group showed better inhibitory activities and selectivity than those with electron-withdrawing groups, and the presence of adjacent dihydroxy in the caffeoyl group was very important for the MMP-2 and MMP-9 inhibitory activities. 相似文献
18.
Yasuhiro Yamada Tomio Emori Shinichi Kinoshita Hirosuke Okada 《Bioscience, biotechnology, and biochemistry》2013,77(3):649-652
(±)-Azetidine-2-carboxylic acid and 3-substituted-2-pyrrolidinones were synthesized from 2-pyrrolidinone via 3-bromo-2-methoxy-1-pyrroline (IIIa). The bromide (IIIa) was obtained by the bromination of 2-methoxy-l-pyrroline using NBS. 相似文献
19.
Chiral (+)- and (?)-enantiomers of (2Z,4E)-5-(1′,2′-epoxy-2′,6′,6′-trimethylcyclohexyl)-3-methyl-2,4-pentadienoic acid have been synthesized from the chiral epoxy alcohols (+)- and (?)-1′,2′-dihydro-1′,2′-epoxy-β-ionone, which were prepared by Katsuki-Sharpless' asymmetric epoxidation of β-cyclogeraniol. The (+)-enantiomer showed strong inhibitory activity in a rice seedling and lettuce germination assay, whereas the (?)-enantiomer was 103-times less active. 相似文献
20.
Wojciech Urjasz Lech Celewicz Krzysztof Golankiewicz 《Nucleosides, nucleotides & nucleic acids》2013,32(6):1189-1202
Abstract A series of 5′-N-methanesulfonyl derivatives of 3′-azido-5′-(alkylamino)-3′,5′-dideoxythymidine was synthesised. The first step of the synthesis involved the reaction of 1-(2,5-dideoxy-5-O-tosyl-β-D-threo-pentofuranosyl)thymine 1 with an appropriate amine to give 1-[5-(alkylamino)-2,5-dideoxy-β-D-threo-pentofuranosyl]thymines 2a-e and 1-(2,5-dideoxy-β-threo-pent-4-enofuranosyl)thymine 3 as a by-product. Compounds 2a-e were treated with an excess of methanesulfonyl chloride to yield intermediates 1-[5-(dimethylamino)-3-O-methanesulfonyl-2,3,5-trideoxy-β-D-threo-pentofuranosyl]-thymine 4a and 1-[5-(N-alkyl-N-methanesulfonyl)-3-O-methanesulfonyl-2,3,5-trideoxy-β-D-threo-penfuranosyl]thymines 4b-e. The reaction of 4a-e with lithium azide in dimethyl-formamide afforded the final compounds 1-[3-azido-5-(N-methyl-N-methanesulfonyl)-2,3,5-trideoxy-β-D-erythro-penofuranosyl]thymine 5a and 1-[3-azido-5-(N-alkyl-N-methanesulfonyl)-2,3,5-trideoxy-β-D-erythro-penofuranosyl]thymines 5b-e. The independent synthesis of 4′,5′-unsaturated product 3 was also described. 相似文献