共查询到20条相似文献,搜索用时 15 毫秒
1.
Zampieri D Mamolo MG Laurini E Scialino G Banfi E Vio L 《Bioorganic & medicinal chemistry》2008,16(8):4516-4522
1-(3,5-Diaryl-4,5-dihydro-1H-pyrazol-4-yl)-1H-imidazole derivatives were synthesized and tested for their in vitro antifungal and antimycobacterial activities. These imidazole derivatives showed an excellent antifungal activity against a clinical strain of Candida albicans and an interesting antitubercular activity against Mycobacterium tuberculosis H(37)Rv reference strain. 相似文献
2.
Isabelle E.J.A. François Bruno P.A. Cammue Sara Bresseleers Hein Fleuren Georges Hoornaert Vaibhav P. Mehta Sachin G. Modha Erik V. Van der Eycken Karin Thevissen 《Bioorganic & medicinal chemistry letters》2009,19(15):4064-4066
We synthesized a family of 3,5-dichloropyrazin-2(1H)-one derivatives and assessed their in vitro fungicidal activity against Candida albicans. Compounds 11 and 20 were most active against C. albicans and induced accumulation of reactive oxygen species in this pathogen. Using a genome-wide approach in the yeast Saccharomyces cerevisiae, we demonstrated that genes involved in vacuolar functionality and DNA-related functions play an important role in cellular mechanisms underlying the fungicidal activity of these compounds. 相似文献
3.
Strappaghetti G Brodi C Giannaccini G Betti L 《Bioorganic & medicinal chemistry letters》2006,16(10):2575-2579
Continuing our research aimed at obtaining new compounds with high affinity and selectivity toward alpha(1)-AR, a new series of arylpiperazine derivatives was designed, synthesized, and biologically tested. The new compounds 1-17 are characterized by a phenylphthalazin-1(2H)-one fragment connected through an alkyl chain to an arylpiperazine residue. The pharmacological profile of these compounds was evaluated for their affinity and selectivity toward alpha(1)-AR, alpha(2)-AR and toward 5HT(1A) serotoninergic receptor. A discussion on the structure-activity relationship (SAR) of these compounds is also reported. 相似文献
4.
Joanna Stefańska Anna Bielenica Marta Struga Stafan Tyski Jerzy Kossakowski Roberta Loddo Cristina Ibba David Collu Esther Marongiu Paolo La Colla 《Central European Journal of Biology》2009,4(3):362-368
Antibacterial and antifungal activity of 10-(diphenylmethylene)-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione derivatives were examined by the disc-diffusion method (growth inhibition zone diameter in agar medium).
The MIC’s for the most active agents were determined. Title compounds were also evaluated in vitro against representatives of different virus classes. Most of the tested compounds exhibit activity against CVB-2 virus. 相似文献
5.
dos Santos MS Oliveira ML Bernardino AM de Léo RM Amaral VF de Carvalho FT Leon LL Canto-Cavalheiro MM 《Bioorganic & medicinal chemistry letters》2011,21(24):7451-7454
A series of 1-aryl-4-(4,5-dihydro-1H-imidazol-2-yl)-1H-pyrazoles (4a–g) and 5-amino-1-aryl-4-(4,5-dihydro-1H-imidazol-2-yl)-1H-pyrazoles (5a–g) were synthesized and evaluated in vitro against three Leishmania species: L. amazonensis, L. braziliensis and L. infantum (L. chagasi syn.). The cytotoxicity was assessed. Among the derivatives examined, six compounds emerged as the most active on promastigotes forms of L. amazonensis with IC50 values ranging from 15 to 60 μM. The reference drug pentamidine presented IC50 = 10 μM. However, these new compounds were less cytotoxic than pentamidine. Based on these results, the more promising derivative 5d was tested further in vivo. This compound showed inhibition of the progression of cutaneous lesions in CBA mice infected with L. amazonensis relative to an untreated control. 相似文献
6.
A series of 2-(indolylmethylidene)-2,3-dihydro-1-benzofuran-3-ones (aurone-indole hybrids) and 2-(indolyl)-4H-chromen-4-ones (flavone-indole hybrids) were designed, synthesized, and their monoamine oxidase (MAO) A and B inhibitory activities were evaluated. Compounds 5b and 11b showed potent inhibitory activities against MAO-A, comparable to that of pargyline used as a positive control, and most of the compounds, except for 2a and 10b, showed potent inhibitory activities against MAO-B. Compound 9a was the most potent and highly selective inhibitor of MAO-B (IC50 value for MAO-B: 0.0026 μM, and MAO-A: >100 μM). Comparison of the inhibitory activities of 1a vs. 9a vs. 13a and 1b vs. 7b vs. 11b suggested that methoxy substitution at R1 on the A-rings of flavonoids increases MAO-A inhibition whereas methoxy substitution at R2 increased MAO-B inhibition. Comparison of 4a vs. 10a, 6a vs. 11a, 3b vs. 8b and 4b vs. 9b showed incremental increases in MAO-B inhibitory activity by R2 substitution on the A ring. Comparison of the MAO-B inhibitory effects of the flavone-indole hybrids and aurone-indole hybrids showed that most of the aurone-indole hybrids were stronger inhibitors than the corresponding flavone-indole hybrids. Molecular docking analysis of compounds 1a and 9a with MAO-B further supported the above structural effects of these compounds on MAO-B inhibitory activity.This is the first report identifying aurone-indole hybrids as potent MAO-B inhibitors. The results reported here suggest that 2-(1H-indol-1-ylmethylene)-6-methoxy-3(2H)-benzofuranone (9a) might be a useful lead for the design and development of novel MAO-B inhibitors 相似文献
7.
Das S Chatterjee N Bose D Dey SK Munda RN Nandy A Bera S Biswas SK Das Saha K 《Cellular physiology and biochemistry》2012,29(1-2):251-260
Different quinazoline derivatives have showed wide spectrum of pharmacological activities. Some 3-(arylideneamino)-phenylquinazoline-4(3H)-ones have been reported to possess antimicrobial activity. The present study has been undertaken to evaluate the anticancer effect of these quinazolinone derivatives. The quinazolinone derivatives were synthesized as reported earlier. Compounds containing NO(2), OH, OCH(3), or OH and OCH(3) as substituent(s) on the arylideneamino group were named as P(3a), P(3b), P(3c), and P(3d) respectively. Out of these, P(3a) and P(3d) showed better cytotoxic activity than P(3b) and P(3c) on a panel of six cancer cell lines of different origin, namely, B16F10, MiaPaCa-2, HCT116, HeLa, MCF7, and HepG2, though the effect was higher in B16F10, HCT116, and MCF7 cells. P(3a) and P(3d) induced death of B16F10 and HCT116 cells was associated with characteristic apoptotic changes like cell shrinkage, nuclear condensation, DNA fragmentation, and annexin V binding. Also, cell cycle arrest at G1 phase, alteration of caspase-3, caspase-9, Bcl-2 and PARP levels, loss of mitochondrial membrane potential, and enhanced level of cytosolic cytochrome c were observed in treated B16F10 cells. Treatment with multiple doses of P(3a) significantly increased the survival rate of B16F10 tumor bearing BALB/c mice by suppressing the volume of tumor while decreasing microvascular density and mitotic index of the tumor cells. 相似文献
8.
Amir Assadieskandar Mohsen Amini Marjan Salehi Hamid Sadeghian Maliheh Alimardani Amirhossein Sakhteman Hamid Nadri Abbas Shafiee 《Bioorganic & medicinal chemistry》2012,20(24):7160-7166
A series of 4,5-diaryl-1H-imidazole-2(3H)-thione was synthesized and their inhibitory potency against soybean 15-lipoxygenase and free radical scavenging activities were determined. Compound 11 showed the best IC50 for 15-LOX inhibition (IC50 = 4.7 μM) and free radical scavenging activity (IC50 = 14 μM). Methylation of SH at C2 position of imidazole has dramatically decreased the 15-LOX inhibition and radical scavenging activity as it can be observed in the inactive compound 14 (IC50 >250 μM). Structure activity similarity (SAS) showed that the most important chemical modification in this series was methylation of SH group and Docking studies revealed a proper orientation for SH group towards Fe core of the 15-LOX active site. Therefore it was concluded that iron chelating could be a possible mechanism for enzyme inhibition in this series of compounds. 相似文献
9.
Amirhossein Sakhteman Alireza Foroumadi Mohammad Sharifzadeh Masoud Amanlou Farhoud Rayatnia Abbas Shafiee 《Bioorganic & medicinal chemistry》2009,17(19):6908-6913
A convenient route for the synthesis of some 2-propen-1-one derivatives with E isomeric configuration is described. The activity of the synthesized compounds was evaluated through behavioral studies of apomorphine-induced licking in animal models. It was demonstrated that most of the synthesized compounds showed moderate activity in inhibition of lickings, among which 6a, was the most active compound at 30 mg/kg. 相似文献
10.
Saladino R Mezzetti M Mincione E Palamara AT Savini P Marini S 《Nucleosides & nucleotides》1999,18(11-12):2499-2510
A convenient and mild synthesis of 5-bromo-N4-substituted-1-(beta-D-arabinofuranosyl)cytosine and 5-bromo-O4-methyl-1-(beta-D-arabinofuranosyl)pyrimidin-2(1H)-one derivatives by selective oxyfunctionalization of the corresponding 4-thionucleosides with 3,3-dimethyldioxirane is reported. The cytotoxicity and the antiviral activity against parainfluenza 1 (Sendai virus) of all new synthesized products are also reported. 相似文献
11.
Antolini M Bozzoli A Ghiron C Kennedy G Rossi T Ursini A 《Bioorganic & medicinal chemistry letters》1999,9(7):1023-1028
A preliminary exploration of analogues of 4,5-bis(3,5-dichlorophenyl)-2-trifluoromethyl-1H-imidazole, 1, as novel antibacterial agents was carried out to determine the basic features of the structure responsible for the observed biological activity. The presence of two aryl rings, the imidazole NH and either a good electron withdrawing group or an aldehyde or amino group at C-2 were required for good levels of activity against methicillin resistant Staphylococcus aureus (MRSA). 相似文献
12.
Park CM Choi JI Choi JH Kim SY Park WK Seong CM 《Bioorganic & medicinal chemistry letters》2011,21(2):698-703
Piperazinyl derivatives of 1-(arylsulfonyl)-2,3-dihydro-1H-quinolin-4-ones have been identified with high binding affinities for 5-HT6 receptor. In particular, 2-methyl-5-(N-methyl-piperazin-1-yl)-1-(naphthalene-2-sulfonyl)-2,3-dihydro-1H-quinolin-4-one (8g) exhibits high binding affinity toward 5-HT6 (IC50 = 8 nM) receptor with good selectivity over other serotonin and dopamine receptors. 相似文献
13.
Zhu HJ Wang JS Donovan JL DeVane CL Gibson BB Markowitz JS 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,846(1-2):351-354
The first HPLC-fluorescence method for the determination of atomoxetine in human plasma was developed and validated. Atomoxetine was derivatized with 4-(4,5-diphenyl-1H-imidazol-2-yl) benzoyl chloride (DIB-Cl) under mild conditions, and separated isocratically on a C18 column using a HPLC system with fluorescence detection (lambdaex: 318 nm, lambdaem: 448 nm). A linear calibration curve was obtained over the concentration range 1-1000 ng/mL (r=0.999). The limit of detection (S/N=3) was 0.3 ng/mL. The relative standard deviations of intra-day and inter-day variations were < or =8.30% and 7.47%, respectively. This method is rapid, sensitive, and suitable for both basic and clinical studies of atomoxetine. 相似文献
14.
Mohsen Nikpour Hamid Sadeghian Mohammad Reza Saberi Reza Shafiee Nick Seyed Mohammad Seyedi Azar Hosseini Heydar Parsaee Alireza Taghian Dasht Bozorg 《Bioorganic & medicinal chemistry》2010,18(2):855-862
Selective PDE3 (phosphodiesterase 3) inhibitors improve cardiac contractility and may be used in congestive heart failure. However, their proarrhythmic potential is the most important side effect. In this work ten new synthetic compounds (3-[(4-methyl-2-oxo-1,2-dihydro-6-quinolinyl)oxy]methylbenzamide analogs: 4a–j) were designed, synthesized and tested for the inhibitory activity against human PDE3A and PDE3B. The strategy of the design was based on the structure of vesnarinone (a selective PDE3 inhibitor) and its docking analysis results. The synthetic compounds showed better PDE3 inhibitory activity in comparison with vesnarinone. Using docking analysis, a common binding model of each compound toward PDE3 was suggested. In the next step the potential cardiotonic activity of the best PDE3A inhibitors (4b, IC50 = 0.43 ± 0.04 μM) was evaluated by using the spontaneously beating atria model. In the experiment, atrium of reserpine-treated rat was isolated and the contractile and chronotropic effects of the synthetic compound were assessed. That was carried out in comparison with vesnarinone. The best pharmacological profile was obtained for the compound 4b, which displayed selectivity for increasing the force of contraction (46 ± 3% change over the control) rather than the frequency rate (16 ± 4% change over the control) at 100 μM. 相似文献
15.
Dong CZ Ahamada-Himidi A Plocki S Aoun D Touaibia M Meddad-Bel Habich N Huet J Redeuilh C Ombetta JE Godfroid JJ Massicot F Heymans F 《Bioorganic & medicinal chemistry》2005,13(6):1989-2007
We have recently reported the discovery of a series of specific inhibitors of human group IIA phospholipase A(2) (hGIIA PLA(2)) to display promising in vitro and in vivo properties. Here we describe the influence of different structural modifications on the specificity and potency against hGIIA PLA(2) versus porcine group IB PLA(2). The SAR results, as well as the logP and pK(a) values of oxadiazolone determined in this work, provide important information towards the comprehension of the mode of action of this kind of compounds. 相似文献
16.
Caruso M Valsasina B Ballinari D Bertrand J Brasca MG Caldarelli M Cappella P Fiorentini F Gianellini LM Scolaro A Beria I 《Bioorganic & medicinal chemistry letters》2012,22(1):96-101
The discovery and characterization of two new chemical classes of potent and selective Polo-like kinase 1 (PLK1) inhibitors is reported. For the most interesting compounds, we discuss the biological activities, crystal structures and preliminary pharmacokinetic parameters. The more advanced compounds inhibit PLK1 in the enzymatic assay at the nM level and exhibit good activity in cell proliferation on A2780 cells. Furthermore, these compounds showed high levels of selectivity on a panel of unrelated kinases, as well as against PLK2 and PLK3 isoforms. Additionally, the compounds show acceptable oral bioavailability in mice making these inhibitors suitable candidates for further in vivo activity studies. 相似文献
17.
Inhibition of amine oxidases activity by 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives
Manna F Chimenti F Bolasco A Secci D Bizzarri B Befani O Turini P Mondovi B Alcaro S Tafi A 《Bioorganic & medicinal chemistry letters》2002,12(24):3629-3633
A novel series of 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives have been synthesised and investigated for the ability to inhibit selectively monoamine oxidases, swine kidney oxidase, and bovine serum amine oxidase. The newly synthesised compounds 1–6 proved to be reversible and non-competitive inhibitors of all types of the assayed amine oxidases. Compounds inhibit monoamine oxidases potently, displaying low I50 values of particular interest. In particular 1-acetyl-3-(2,4-dihydroxyphenyl)-5-(3-methylphenyl)-4,5-dihydro-(1H)-pyrazole 6 showed to be a potent monoamine oxidase inhibitor with a Ki of about 10−8 M. Further insights in the theoretical evaluation of the possible interactions between the compounds and monoamine oxidase B have been developed through a computational approach. 相似文献
18.
Xin-Hua Liu Jing Zhu An-na Zhou Bao-An Song Hai-Liang Zhu Lin-Shan bai Pinaki S. Bhadury Chun-Xiu Pan 《Bioorganic & medicinal chemistry》2009,17(3):1207-1213
A series of new 2-(1-(2-(substituted-phenyl)-5-methyloxazol-4-yl)-3-(2-substitued-phenyl)-4,5-dihydro-1H-pyrazol-5-yl)-7-substitued-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized. The results showed that compounds 9q and 10q can strongly inhibit Staphylococcus aureus DNA gyrase and Bacillus subtilis DNA gyrase (with IC50s of 0.125 and 0.25 μg/mL against S. aureus DNA gyrase, 0.25 and 0.125 μg/mL against B. subtilis DNA gyrase). On the basis of the biological results, structure–activity relationships were also discussed. 相似文献
19.
Dengyou Zhang Jing Ai Zhongjie Liang Wei Zhu Xia Peng Xianjie Chen YinChun Ji Hualiang Jiang Cheng Luo Meiyu Geng Hong Liu 《Bioorganic & medicinal chemistry letters》2013,23(8):2408-2413
A series of novel 5-(benzyloxy)pyridin-2(1H)-ones were designed, synthesized and biologically evaluated for c-Met inhibition. Various amides and benzoimidazoles at C-3 position were investigated. A potent compound 12b with a c-Met IC50 of 12 nM was identified. This compound exhibited potent inhibition of EBC-1 cell associated with c-Met constitutive activation and showed high selectivity for c-Met than other tested 11 kinases. The binding model 12b with c-Met was disclosed by docking analysis. 相似文献
20.
Burguete A Pontiki E Hadjipavlou-Litina D Villar R Vicente E Solano B Ancizu S Pérez-Silanes S Aldana I Monge A 《Bioorganic & medicinal chemistry letters》2007,17(23):6439-6443
We report the synthesis, anti-inflammatory and antioxidant activities of novel ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives and of their 4,5-dihydro-(1H)-pyrazole analogues. The tested compounds inhibit the carrageenin-induced rat paw edema (4.5-56.1%) and present important scavenging activities. Compound 2a is the most potent (56.1%) in the in vivo experiment and exhibits promising in vitro inhibition of soybean lipoxygenase (IC(50)<1microM). 相似文献