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1.
Iminoalditol analogues of galactofuranosides were synthesized from 1-C-(2′-oxo-propyl)-1,4-dideoxy-1,4-imino-d-galactosides and different amines by reductive amination, followed by removal of protecting groups. The activity of these compounds against galactosidases and other glycosidases was investigated. The best inhibitor against β-galactosidase (bovine liver) is a diastereomeric mixture of an iminoalditol (10h), which contains a hydrophobic hexadecyl aglycon (R = C16H33), whereas no significant inhibitory activity was observed with compounds having a hydrophilic aglycon. Surprisingly, activation of α-galactosidase (coffee bean) by 10h was also observed. Because these results were obtained from a mixture of iminoalditols, the inhibition and activation of glycosidases could result from different diastereomers. 相似文献
2.
Takayama W Shirasaki Y Sakai Y Nakajima E Fujita S Sakamoto-Mizutani K Inoue J 《Bioorganic & medicinal chemistry letters》2003,13(19):3273-3276
A novel series of benzothiazolylidenehydroxamic acid derivatives has been designed and synthesized as PDF inhibitors. Some of this novel class of PDF inhibitors exhibited micromolar order enzyme inhibitory activity and antibacterial activity. 相似文献
3.
Wei Tian Guangqian Han Ju Zhu Jingjing Qi Qianqian Chen Juntao Zhao Canhui Zheng Ling Zhang Youjun Zhou Jiaguo Lv 《Bioorganic & medicinal chemistry letters》2013,23(14):4177-4184
A series of novel 5-phenyl-1H-pyrazole-3-carboxylic acid amide derivatives were designed, synthesized, and their acrosin inhibitory activities in vitro were evaluated. The results of the acrosin inhibitory activity showed that all target compounds were more potent than control TLCK. Compounds AQ-A1, AQ-D3, AQ-D4, AQ-E4 and AQ-E5 exhibited stronger acrosin inhibitory activities than control ISO-1. Especially, compound AQ-E5 displayed the most potent acrosin inhibitory activity in all the compounds, with an IC50 of 0.01 μmol/mL. This study provided a new structural class for the development of novel acrosin inhibitory agents. 相似文献
4.
Dharmarajan Sriram Perumal Yogeeswari Prathiba Dhakla Palaniappan Senthilkumar Debjani Banerjee Thimmappa H. Manjashetty 《Bioorganic & medicinal chemistry letters》2009,19(4):1152-1154
Eighteen 5-nitrofuran-2-yl derivatives were prepared by reacting 5-nitro-2-furfural with various (sub)phenyl/pyridyl thiosemicarbazide using microwave irradiation. The compounds were tested for their in vitro activity against tubercular and various non-tubercular mycobacterium species in log-phase and 6-week-starved cultures. Compound N-(3,5-dibromopyridin-2-yl)-2-((5-nitrofuran-2-yl)methylene)hydrazinecarbothioamide (4r) was found to be the most potent compound (MIC: 0.22 μM) and was 3 times more active than standard isoniazid (INH) and equally active as rifampicin (RIF) in log-phase culture of Mycobacterium tuberculosis H37Rv. In starved M. tuberculosis H37Rv, 4r inhibited with MIC of 13.9 μM and was found to be 50 times more active than INH and slightly more active than RIF. 相似文献
5.
Wang J Elchert B Hui Y Takemoto JY Bensaci M Wennergren J Chang H Rai R Chang CW 《Bioorganic & medicinal chemistry》2004,12(24):4232-6413
The synthesis of a library of trehalose-based compounds has been accomplished, and their activities against Mycobacterium smegmatis have been determined. A preliminary structure–activity relationship (SAR) is reported. Despite not having a potent lead, one of the trehalose derivatives displays strong activity when applied with isoniazid (INH), which is known to have low sterilizing activity. The bacteriocidal nature of our compounds against Mycobacterium may be significant for the development of new therapies against tuberculosis. 相似文献
6.
Jew SS Park BS Lim DY Kim MG Chung IK Kim JH Hong CI Kim JK Park HJ Lee JH Park HG 《Bioorganic & medicinal chemistry letters》2003,13(4):609-612
Twenty-one pyridine-2-carboxylate derivatives were prepared by the coupling of 6-formyl-2-carboxylic acid with the corresponding phenol, thiophenol, and aniline, substituted with various functional groups. Among them, the 3,4-dichlorothiophenol ester (9p) showed the highest in vitro telomerase inhibitory activity and quite significant in vivo tumor suppression activity. 相似文献
7.
M Shinada F Narumi Y Osada K Matsumoto T Yoshida K Higuchi T Kawasaki H Tanaka M Satoh 《Bioorganic & medicinal chemistry》2012,20(16):4901-4914
Phenserine is a potentially attractive drug for Alzheimer's disease. In order to further expand SAR study for inhibitions of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), the methyl group at the 3a-position of phenserine was replaced with an alkyl or alkenyl group, and its phenylcarbamoyl moiety was substituted at the o- or p-position. The synthetic methodology for these phenserine analogues includes the efficient cascade reactions for introduction of the 3a-substituent and assembly of the quaternary carbon center followed by reductive cyclization to the key pyrroloindoline structure. The bulkiness of the substituent at 3a-position of phenserine derivatives tends to reduce the inhibitory effect on AChE activity in the following order: methyl>ethyl>vinyl>propyl≈allyl>reverse-prenyl groups. Among the series synthesized, the 3a-ethyl derivative demonstrated the highest AChE selectivity. In construct, the 3a-reverse-prenyl derivative indicated modest BuChE selectivity. 相似文献
8.
The synthesis of a series of andrographolide derivatives was described and their inhibitory effects on TNF-α and IL-6 secretion in mouse macrophages were also evaluated. Most of the tested compounds showed inhibitory effects, and the compounds with the structure of 12-hydroxy-14-dehydroandrographolide showed better inhibitory activity than the compounds with the structure of isoandrographolide. 相似文献
9.
Yasuhiro Horita Takemasa Takii Taku Chiba Ryuji Kuroishi Yasuhiro Maeda Yukihisa Kurono Emi Inagaki Kenji Nishimura Yoshifumi Yamamoto Chiyoji Abe Masami Mori Kikuo Onozaki 《Bioorganic & medicinal chemistry letters》2009,19(22):6313-6316
A series of sugar derivatives (1–13) were synthesized and evaluated for antibacterial activity against Mycobacterium tuberculosis (MTB), especially multi-drug resistant (MDR) MTB, and the structure–activity relationships of these compounds were studied. The results showed that the compound OCT313 (2-acetamido-2deoxy-β-d-glucopyranosyl N,N-dimethyldithiocarbamate) (4) exhibited significant in vitro bactericidal activity, and that the dithiocarbamate group at C-1 position of the glucopyranoside ring was requisite for the antibacterial activity. 相似文献
10.
Tabersonine, the main alkaloid in Voacanga seeds, was used as a lead compound to semi-synthesize tabersonine derivatives. In total, 13 compounds, containing 10 novel tabersonine derivatives, were synthesized by introducing substituent groups R1–R5. The acetylcholinesterase (AChE) inhibitory activities of tabersnonine derivatives were evaluated using Ellman’s method. Among them, compound (7) showed the highest AChE inhibitory activity with the IC50 value was 5.32 μM. The substituent groups R1–R5 showed different influences on the AChE inhibitory activities of tabersonine derivatives. The AChE inhibitory activities of tabersonine derivatives increased with the introduction of group R1 and/or combined groups R3, R4, while decreased with the introduction of group R5. And the group R2 showed no significant influence on the AChE inhibitory activities of tabersonine derivatives. 相似文献
11.
Bessy Gutiérrez Christian Muñoz Luis Osorio Krisztina Fehér Tünde-Zita Illyés Zsuzsa Papp Ambati Ashok Kumar Katalin E. Kövér Hernán Sagua Jorge E. Araya Patricio Morales László Szilágyi Jorge González 《Bioorganic & medicinal chemistry letters》2013,23(12):3576-3579
Aromatic oligovalent glycosyl disulfides and some diglycosyl disulfides were tested against three different Trypanosoma cruzi strains. Di-(β-d-galactopyranosyl-dithiomethylene) benzenes 2b and 4b proved to be the most active derivatives against all three strains of cell culture-derived trypomastigotes with IC50 values ranging from 4 to 11 μM at 37 °C. The inhibitory activities were maintained, although somewhat lowered, at a temperature of 4 °C as well. Three further derivatives displayed similar activities against at least one of the three strains. Low cytotoxicities of the active compounds, tested on confluent HeLa, Vero and peritoneal macrophage cell cultures, resulted in significantly higher selectivity indices (SI) than that of the reference drug benznidazole. Remarkably, several molecules of the tested panel strongly inhibited the parasite release from T. cruzi infected HeLa cell cultures suggesting an effect against the intracellular development of T. cruzi amastigotes as well. 相似文献
12.
Junsang Lee Bong Soo Nam Hwan Kim Chang-Hyun Oh So Ha Lee Seung Joo Cho Tae Bo Sim Jung-Mi Hah Dong Jin Kim Jinsung Tae Kyung Ho Yoo 《Bioorganic & medicinal chemistry letters》2010,20(19):5722-5725
The synthesis of a novel series of aminoquinazoline derivatives 1a–r and their antiproliferative activities against A375 human melanoma cell line were described. Among them, six compounds showed superior antiproliferative activities to Sorafenib as a reference compound. In particular, the representative compound 1q bearing chromen-4-one moiety exhibited excellent antiproliferative activity (IC50 = 0.006 μM) and good selectivity over HS27 fibroblast cell line. 相似文献
13.
Plaunotol, a known antiulcer drug, has antibacterial activities against Helicobacter pylori. Plaunotol thiourea derivatives 2--4 and diol derivatives 6--10 were designed in search for a compound with high antibacterial activities. Thiourea derivatives 2--4 were synthesized regioselectively using our effective synthetic route for plaunotol (1), and diol derivatives 6--10 were also synthesized. Their antibacterial activities against H. pylori are described and we found that the most potent antibacterial agent was C1-thiourea derivative 2c. 相似文献
14.
Cho JC Rho HS Joo YH Lee CS Lee J Ahn SM Kim JE Shin SS Park YH Suh KD Park SN 《Bioorganic & medicinal chemistry letters》2012,22(12):4159-4162
We synthesized benzoate ester derivatives of kojic acid with and without adamantane moiety. Benzoate derivatives 2a-e that did not contain an adamantane moiety showed potent tyrosinase inhibitory activities. However, depigmenting activity was not noted in a cell-based assay. Contrasting results were obtained for benzoate derivatives (3a-e) containing an adamantane moiety. Compounds 3a-e showed potent depigmenting activities without tyrosinase inhibitory activities. To the best of our knowledge, this is the first study showing the depigmenting activities of kojic acid derivatives without tyrosinase inhibitory activities. 相似文献
15.
《Bioorganic & medicinal chemistry》2020,28(15):115596
Gallic acid (GA), a natural phenolic acid, has received numerous attention because of its anti-oxidative, anti-inflammatory, and anti-cancer activity. More importantly, GA can act as an efficient inhibitor of α-Synuclein (α-Syn) aggregation at early stages. Nevertheless, some evidences suggest that GA is unlikely to cross the blood–brain barrier because of its high hydrophilicity. Hence, GA may not be considered as a promising candidate or entering brain and directly affecting the central nervous system. Accordingly, we have designed and synthesized a series of amide derivatives of GA, some of which possess appropriate lipophilicity and hydrophilicity with LogP (2.09–2.79). Meanwhile, these sheet-like conjugated compounds have good π-electron delocalization and high ability of hydrogen-bond formation. Some compounds have shown better in vitro anti-aggregation activities than GA towards α-Syn, with IC50 down to 0.98 μM. The valid modification strategy of GA is considered an efficient way to discover novel inhibitors of α-Syn aggregation. 相似文献
16.
Yoshihiro Noguchi Yuri Yasuda Makoto Tashiro Tadashi Kataoka Yoshiaki Kitamura Mahmoud Kandeel Yukio Kitade 《Parasitology international》2013,62(4):368-371
Plasmodium falciparum thymidylate kinase (PfTMK) is a promising antimalarial target due to its unique substrate specificity. Recently, we reported that 2′,3′-dideoxycarbocyclic thymidine showed moderate inhibitory activity and reported the related structure–activity relationship for inhibitors against PfTMK. In this study, we have designed and synthesized enantioselective 2′,3′-dideoxycarbocyclic pyrimidine nucleosides based on our previous results and screened them for inhibitory activity against PfTMK. The most potent inhibitor showed KiTMP and KidGMP values of 14 and 20 μM, respectively. The fluorinated dideoxy derivative (-)-7, exhibited lower KiTMP and higher KidGMP compared with that of the parent compound (KiTMP, KidGMP equals 20 and 7 μM, respectively). The modification of carbocyclic pyrimidine nucleosides is a promising strategy for developing powerful PfTMK inhibitors. 相似文献
17.
The syntheses of nine S-alkylated, cyclic sulfonium-ions with varying alkyl chain lengths, as mimics of N-alkylated imino sugars, and their glucosidase inhibitory activities are described. The target compounds were synthesized by alkylation of 2,3,5-tri-O-benzyl-1,4-anhydro-4-thio-d-arabinitol at the ring sulfur atom using various alkyl halides, followed by deprotection using boron trichloride. Enzyme inhibitory assays against recombinant human maltase glucoamylase (MGA), a critical enzyme in the small intestine involved in the breakdown of glucose oligosaccharides into glucose itself, shows that they are effective inhibitors of MGA with K(i) values ranging from 6 to 75 microM. 相似文献
18.
《Bioorganic & medicinal chemistry》2019,27(20):114918
Twelve N-hydroxycinnamoyl amino acid amide ethyl esters (CAES) were synthesized by using l-amino acid ethyl ester hydrochloride and corresponding cinnamic acid (ferulic acid, acetylferulic acid and caffeic acid) as raw materials in the presence of a catalytic amount of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide-hydrochloride (EDC) and 1-hydroxybenzotriene (HOBt). The 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activities of CAES were evaluated. The anti-tyrosinase activities of N-feruloyl amino acid ethyl esters and the hydroxyl (OH) free radical scavenging activities of N-caffeoyl amino acid ethyl esters were also examined. DPPH free radical scavenging activity was shown in all CAES, of which N-caffeoyl amino acid ethyl esters demonstrated higher radical scavenging activity than N-feruloyl amide derivatives, and (E) -N-(caffeic acid)-l-glycinate ethyl ester (c5) had the strongest ability to scavenge free radicals with an IC50 value of 18.6 µM. The acetylferuloyl amino acid esters exhibited the highest tyrosinase inhibition activity among the tested amides. 相似文献
19.
Ring-C of oleanolic acid was chemically modified by treating with NBS under a variety of experimental conditions. The structures of the synthesized compounds were established by spectral analysis (1H &13C NMR and Mass). All the compounds were evaluated against a panel of five human cancer cell lines by using MTT assay. Among the tested compounds, 2 and 7 showed significant activity against breast cancer cell line, MCF-7. Most significantly, compound 7 showed several folds enhanced activity against MCF-7 cancer cell lines (IC50: 2.96 μM) than that of the parent (1) and the intermediate compound (6). Flow cytometric analysis revealed that these compounds arrested the cell cycle in G0/G1 phase and induced mitochondrial mediated apoptosis. 相似文献
20.
Bart I. Roman Sigrid Verhasselt Christophe W. Mangodt Olivier De Wever Christian V. Stevens 《Bioorganic & medicinal chemistry letters》2018,28(13):2261-2264
(S)-Blebbistatin is a micromolar myosin II ATPase inhibitor that is extensively used in research. In search of analogs with improved potency, we have synthesized for the first time C-ring modified analogs. We introduced hydroxymethyl or allyloxymethyl functionalities in search of additional favorable interactions and a more optimal filling of the binding pocket. Unfortunately, the resulting compounds did not significantly inhibit the ATPase activity of rabbit skeletal-muscle myosin II. This and earlier reports suggest that rational design of potent myosin II inhibitors based on the architecture of the blebbistatin binding pocket is an ineffective strategy. 相似文献