共查询到20条相似文献,搜索用时 15 毫秒
1.
Chen SH Sun X Boyer R Paschal J Zeckner D Current W Zweifel M Rodriguez M 《Bioorganic & medicinal chemistry letters》2000,10(18):2107-2110
A series of aliphatic side-chain analogues of pseudomycin was synthesized and evaluated during the course of our side-chain SAR effort. We found that several of the pseudomycin side-chain analogues (e.g., 10) exhibited good in vitro activity against all three major fungi responsible for systemic fungal infections. 相似文献
2.
Jamison J Levy S Sun X Zeckner D Current W Zweifel M Rodriguez M Turner W Chen SH 《Bioorganic & medicinal chemistry letters》2000,10(18):2101-2105
We have described herein the syntheses of three novel series of aromatic ring containing pseudomycin side-chain analogues. Preliminary biological evaluations of these analogues clearly indicate that it is possible to synthesize rigid pseudomycin side-chain analogues without compromising in vitro antifungal activity. 相似文献
3.
X Sun D Zeckner Y Zhang R K Sachs W L Current M Rodriguez S H Chen 《Bioorganic & medicinal chemistry letters》2001,11(14):1881-1884
With the aim of identifying safer pseudomycin derivatives, we synthesized and evaluated a number of N-acyloxymethyl carbamate linked prodrugs of 3-amido pseudomycin analogues. To our satisfaction, all of the prodrug-amide combinations prepared exhibited good in vivo efficacy against murine Candidiasis. When evaluated in a dose elevation study, all of the newly synthesized combinations (e.g., 4A, 6A, 8A, and 8B) demonstrated improved toxicity profiles in comparison to their corresponding 3-amides as well as the parent pseudomycin B. 相似文献
4.
Zhang YZ Sun X Zeckner DJ Sachs RK Current WL Gidda J Rodriguez M Chen SH 《Bioorganic & medicinal chemistry letters》2001,11(7):903-907
As a result of our core SAR effort, we discovered a large number of 3-amido pseudomycin B (PSB) analogues (e.g., 4e LY448212 and 5b LY448731) that retain good in vitro and in vivo (IP) activities against Candida and Cryptococcus without inherent tail vein irritation. Several dimethylamino termini bearing 3-amides (e.g., 5b) also exhibited improved potency against Aspergillus in vitro. When evaluated in a two-week rat toxicology study, it was found that all animals receiving 4e (up to 75 mg/kg) were found to be normal. On the basis of these observations, we are convinced that it is possible to broaden the antifungal spectrum and improve the safety profile of pseudomycin analogues at the same time. 相似文献
5.
Rodriguez MJ Belvo M Morris R Zeckner DJ Current WL Sachs RK Zweifel MJ 《Bioorganic & medicinal chemistry letters》2001,11(2):161-164
The gamma hydroxyl present in the aliphatic side chain of the natural products pseudomycin A and C' provided a unique handle for the pH dependent side-chain deacylation. Low pH reaction conditions were used to cleave the side chain with minimal degradation of the peptide core. The pseudomycin nucleus intermediate obtained from the deacylation of pseudomycin A was pivotal in the synthesis of novel side-chain analogues. A practical synthesis of a minor fermentation factor pseudomycin C' and related analogues is reported. 相似文献
6.
Krishnamurthy M Ferreira AM Moore BM 《Bioorganic & medicinal chemistry letters》2003,13(20):3487-3490
A series of novel phenyl substituted side-chain analogues of classical cannabinoids were synthesized and their CB1 and CB2 binding affinities were evaluated relative to Delta(8)-THC and compound 2. CB1 and CB2 binding assays indicate that the dimethyl and ketone analogues (3) and (6) display selectivity for the CB2 receptor in comparison to delta(8)-THC and compound 2. This study provides newer insights into the geometrical and functional group requirements of the ligand binding pockets of the CB1 and the CB2 receptors. 相似文献
7.
Novel 3′-N-tert-butylsulfonyl analogues 10a–c of docetaxel were synthesized and their biological evaluation in cytotoxicity in vitro against several human tumor cell lines were presented. The biologically tested results showed that N-oxide pyridyl substituted10b–c had potent cytotoxicities against human tumor cell lines Eca-109, SKOV3, SMMC-7721, HCT-8, PC3, MCF-7, HeLa and KB. 相似文献
8.
《Bioorganic & medicinal chemistry letters》2014,24(7):1672-1676
In this work, nineteen analogues of Agomelatine were readily synthesized through structural modification of the acetamide side-chain starting from the key common intermediate 2-(7-methoxynaphthalen-1-yl) ethanamine (3), which was prepared from commercially available compound 2-(7-methoxynaphthalen-1-yl) acetonitrile (2) in two steps. Corticosterone-induced PC12 pheochromocytoma cells phenotypic in vitro model was utilized to evaluate their potential antidepression activities. Imide compound 4a and acylamino carboxylic acid analogue 5b showed good protective effects on traumatic PC12 cells with protection rates of 34.2% and 23.2%, respectively. Further in vivo assessments in C57 mice FST (forced swim test) model demonstrated that compound 4a significantly reduced the immobility time of the tested subjects, indicating antidepressant-like activity. Preliminary toxicity assays conducted on human normal liver L02 cells and embryonic kidney 293 cells suggested a relatively low safety risk for compound 4a compared with the marketed drugs Agomelatine and Fluoxetine. The promising antidepressant-like efficacy of compound 4a, together with the relatively low toxicity to the normal tested cells and high liability of diffusion through the blood–brain barrier (BBB), presents us insights of exploration of me-better drug candidates of Agomelatine. 相似文献
9.
Leixiang Yang Jingxu Gong Feng Wang Yongmin Zhang Yanguang Wang Xiaojiang Hao 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):399-404
In this work, we evaluated the antioxidant properties of the eight novel silybin analogues for their capacity to scavenge free radicals including superoxide anion radicals and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals in vitro. Compound 7d demonstrated an excellent antioxidant effect in scavenging superoxide anion free radical with an IC50 value of 26.5 μM, while the IC50 of quercetin (the reference compound) was 38.1 μM. Compounds 7b, 7e, 7h showed certain scavenging activities for both types of free radicals. 相似文献
10.
Ya-Li Song Yun-Fang Dong Tao Yang Chao-Chao Zhang Li-Min Su Xin Huang Dong-Nuan Zhang Geng-Liang Yang Yu-Xin Liu 《Bioorganic & medicinal chemistry》2013,21(24):7624-7627
In an effort to develop potent anti-cancer chemopreventive agents that act on topoisomerase II, a novel series of bisindolylalkanes analogues such as 3,3′-(thiochroman-4,4-diyl)bis(1H-indole) are synthesized. Structures of all compounds are elucidated by 1H NMR, 13C NMR and HRMS. Anti-proliferative activities for all of these compounds are investigated by the method of MTT assay on 7 human cancer lines. Most of them showed antitumor activities in vitro, the half maximal inhibitory concentration (IC50) value is 7.798 μg/mL of 3a against MCF7. Compound 3a showed comparable topoisomerase II inhibitory activity to etoposide (VP-16) at 100 μM concentration. The rest of the compounds also showed varying degree topoisomerase II inhibitory activity. 相似文献
11.
Synthesis and biological evaluation of novel PDMP analogues 总被引:1,自引:0,他引:1
Hillaert U Boldin-Adamsky S Rozenski J Busson R Futerman AH Van Calenbergh S 《Bioorganic & medicinal chemistry》2006,14(15):5273-5284
A new series of hybrid PDMP analogues, based both on PDMP and styryl analogues of natural ceramide, has been synthesized from D-serine. The synthetic route was developed such that future introduction of different aryl groups is straightforward. Biological evaluation, both in vitro on rat liver Golgi fractions as well as in HEK-293 and COS-7 cells, revealed two lead compounds with comparable inhibitory potency as PDMP, which could be elaborated to more potent inhibitors. 相似文献
12.
Yang L Gong J Wang F Zhang Y Wang Y Hao X Wu X Bai H Stöckigt J Zhao Y 《Journal of enzyme inhibition and medicinal chemistry》2006,21(4):399-404
In this work, we evaluated the antioxidant properties of the eight novel silybin analogues for their capacity to scavenge free radicals including superoxide anion radicals and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals in vitro. Compound 7d demonstrated an excellent antioxidant effect in scavenging superoxide anion free radical with an IC50 value of 26.5 microM, while the IC50 of quercetin (the reference compound) was 38.1 microM. Compounds 7b, 7e, 7h showed certain scavenging activities for both types of free radicals. 相似文献
13.
Michael S. Christodoulou Nikolas Fokialakis Daniele Passarella Aída Nelly García-Argáez Ornella Maria Gia Ingemar Pongratz Lisa Dalla Via Serkos A. Haroutounian 《Bioorganic & medicinal chemistry》2013,21(14):4120-4131
A collection of compounds, structurally related to the anticancer drug tamoxifen, used in breast cancer therapy, were designed and synthesized as potential anticancer agents. McMurry coupling reaction was used as the key synthetic step in the preparation of these analogues and the structural assignment of E, Z isomers was determined on the basis of 2D-NOESY experiments. The compounds were evaluated for their antiproliferative activity on breast cancer (MCF-7), cervix adenocarcinoma (HeLa) and biphasic mesothelioma (MSTO-211H) human tumor cell lines. The estrogen like properties of the novel compounds were compared with those of the untreated controls using an estrogen responsive element-based (ERE) luciferase reporter assay and compared to 17β-estradiol (E2). Finally, with the aim to correlate the antiproliferative activity with an intracellular target(s), the effect on relaxation activity of DNA topoisomerases I and II was assayed. 相似文献
14.
Chabane H Lamazzi C Thiery V Pierre A Leonce S Pfeiffer B Renard P Guillaumet G Besson T 《Journal of enzyme inhibition and medicinal chemistry》2003,18(2):167-174
Novel thiazolocarbazole derivatives have been synthesized via the corresponding imino-1,2,3-dithiazoles. In vitro antitumor activity of these polyheterocyclic compounds was studied. 相似文献
15.
Paterson I Gardner NM Poullennec KG Wright AE 《Bioorganic & medicinal chemistry letters》2007,17(9):2443-2447
Novel analogues of the microtubule-stabilising agent dictyostatin were designed using existing SAR information from the structurally related discodermolide, synthesised by a late-stage diversification strategy and evaluated in vitro for growth inhibition against a range of human cancer cell lines, including those known to exhibit Taxol-resistance (AsPC-1, DLD-1, PANC-1, NCI/ADR). 相似文献
16.
《Bioorganic & medicinal chemistry letters》2020,30(16):127286
Natural quinones and their analogues have attracted growing attention because of their novel anticancer activities. A series of novel isothiazoloquinoline quinone analogues were synthesized and evaluated for antitumor activities against four different kind of cancer cells. Among them, isothiazoloquinolinoquinones inhibited cancer cells proliferation effectively with IC50 values in the nanomolar range, and isothiazoloquinolinoquinone 13a induced the cell apoptosis. Further exploration of possible mechanism of action indicates that 13a not only activates ROS production through NQO1-directed redox cycling but also inhibits the phosphorylation of STAT3. These findings indicate that 13a has potential use for the development of new skeleton drug candidate as an efficient substrate of NQO1 and STAT3 inhibitor. 相似文献
17.
Synthesis and pharmacological evaluation of novel non-lactone analogues of camptothecin 总被引:3,自引:0,他引:3
Hautefaye P Cimetière B Pierré A Léonce S Hickman J Laine W Bailly C Lavielle G 《Bioorganic & medicinal chemistry letters》2003,13(16):2731-2735
Ten novel camptothecin (CPT) derivatives devoid of the lactone function in the E-ring were synthesized and evaluated as anticancer agents. Several of these CPT analogues bearing a five-membered E-ring are potent inhibitors of the DNA relaxation and cleavage reactions catalyzed by topoisomerase I and exhibit promising cytotoxic activities with IC(50) values in the nM range. This is the first successful design of lactone-free CPT, providing thus a new avenue to the development of topoisomerase I targeted antitumor agents. 相似文献
18.
Grotenbreg GM Spalburg E de Neeling AJ van der Marel GA Overkleeft HS van Boom JH Overhand M 《Bioorganic & medicinal chemistry》2003,11(13):2835-2841
The synthesis of novel gramicidin S analogues having additional functionalities in the turn region by employing a biomimetic approach is described. The preservation of beta-sheet character in all analogues was established by NMR and the biological activity was evaluated. 相似文献
19.
Chatgilialoglu C Ferreri C Gimisis T Roberti M Balzarini J De Clercq E 《Nucleosides, nucleotides & nucleic acids》2004,23(10):1565-1581
Novel anomeric spironucleosides and 1'-cyano-2',3'-didehydro-2',3'-dideoxyuridine, a structural analogue of known anti-HIV agents, were prepared by nucleophilic addition of organolithium reagents to 1'-cyano-2'-deoxy- and 1'-cyano-2'-deoxy-2'beta-bromo-uridine derivatives, respectively. The yield and distribution of products depended on the reaction conditions, which were studied in detail. Although none of the compounds exhibited antiviral activity, two compounds displayed cytostatic activity against both murine leukemia and human T-lymphocyte cells. 相似文献
20.
Joon Hee Hong So-Young Kim Chang-Hyun Oh Kyung Ho Yoo Jung-Hyuck Cho Prof. Dr. 《Nucleosides, nucleotides & nucleic acids》2013,32(3):341-350
Novel acyclic nucleoside analogues were designed and synthesized as open-chain analogues of neplanocin A. The coupling of the allylic bromide with purine bases using cesium carbonate afforded a series of novel acyclic nucleosides. The synthesized compounds Ia – II were evaluated for their antiviral activity against various viruses such as HIV, HSV-1, HSV-2, and ECMV. 相似文献