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31.
32.
Sung Nim Han Jean-Marc Zingg Mohsen Meydani 《Archives of biochemistry and biophysics》2010,495(1):49-55
Mice were supplemented with low and high doses of natural and synthetic vitamin E, T cells from the spleen isolated and stimulated with plate-bound anti-CD3 and soluble anti-CD28, and gene expression changes assessed by gene array experiments. The data obtained indicate significant qualitative and quantitative differences between the two vitamin forms in regulating gene expression in response to T-cell stimulation. Marker genes have been found whose expression can be considered significant in establishing the level of, and response to vitamin E for both natural and synthetic vitamin E supplementation; unique markers for synthetic vitamin E supplementation and unique markers for natural vitamin E supplementation have been identified. 相似文献
33.
34.
Suk Youn Kang Eun-Jung Park Woo-Kyu Park Hyun Jung Kim Daeyoung Jeong Myung Eun Jung Kwang-Seop Song Suk Ho Lee Hee Jeong Seo Min Ju Kim MinWoo Lee Ho-Kyun Han Eun-Jung Son Ae Nim Pae Jeongmin Kim Jinhwa Lee 《Bioorganic & medicinal chemistry letters》2010,20(5):1705-1711
Arylpiperzine-containing pyrrole 3-carboxamide derivatives were synthesized and evaluated as novel antidepressant compounds. The various analogues were efficiently prepared and bio-assayed for binding to 5-HT2A, 5-HT2C receptor, and 5-HT transporter. Based on their in vitro and in vivo activities as well as selectivity over other neurotransmitter receptors and PK profiles, 33 and 34 were identified as lead compounds. Consequently, this pyrrole series of compounds appears to be promising enough to warrant further investigation. 相似文献
35.
Kim JY Kim D Kang SY Park WK Kim HJ Jung ME Son EJ Pae AN Kim J Lee J 《Bioorganic & medicinal chemistry letters》2010,20(22):6439-6442
Pyrimidine usually has good pharmacokinetic properties as a drug substance and considerable efforts have been devoted to develop pyrimidine derivatives into drug candidates. Arylpiperazine-containing pyrimidine 4-carboxamide derivatives were synthesized and evaluated for binding to serotonin receptors and transporter. Pyrimidine derivatives showed good antidepressant activity in FST (forced swimming test) animal model and also displayed no appreciable inhibitory activity against hERG channel blocking assay. Herein SAR studies of pyrimidine derivatives targeting serotonin receptors and transporter will be disclosed. 相似文献
36.
Euna Yoo Juhee Yoon Ae Nim Pae Hyewhon Rhim Woo-Kyu Park Jae Yang Kong Hea-Young Park Choo 《Bioorganic & medicinal chemistry》2010,18(4):1665-1675
A novel series of 5-HT2A ligands that contain a (phenylpiperazinyl-propyl)arylsulfonamides skeleton was synthesized. Thirty-seven N-(cycloalkylmethyl)-4-methoxy-N-(3-(4-arylpiperazin-1-yl)propyl)-arylsulfonamide and N-(4-(4-arylpiperazin-1-yl)butan-2-yl)-arylsulfonamide compounds were obtained. The binding of these compounds to the 5-HT2A, 5-HT2C, and 5-HT7 receptors was evaluated. Most of the compounds showed IC50 values of less than 100 nM and exhibited high selectivity for the 5-HT2A receptor. Among the synthesized compounds, 16a and 16d showed good affinity at 5-HT2A (IC50 = 0.7 nM and 0.5 nM) and good selectivity over 5-HT2C (50–100 times) and 5-HT7 (1500–3000 times). 相似文献
37.
Myung-Hee Son Ji Young Kim Eun Jeong Lim Du-Jong Baek Kihang Choi Jae Kyun Lee Ae Nim Pae Sun-Joon Min Yong Seo Cho 《Bioorganic & medicinal chemistry letters》2013,23(5):1472-1476
We described here the synthesis and biological evaluation of mGluR5 antagonists containing a quinoline ring structure. Using intracellular calcium mobilization assay (FDSS assay), we identified compound 5n, showing high inhibitory activity against mGluR5. In addition, it was found that compound 5n has excellent stability profile. Finally, this compound exhibited favorable analgesic effects in spinal nerve ligation model of neuropathic pain, which is comparable to gabapentin. 相似文献
38.
Doddareddy MR Thorat DA Seo SH Hong TJ Cho YS Hahn JS Pae AN 《Bioorganic & medicinal chemistry》2011,19(5):1714-1720
Structure based drug design (SBDD) was used to discover heat shock protein 90 (HSP90) inhibitors useful in the treatment of cancer. By using the crystal structure of HSP90-ligand complex (1uyi), a docking model was prepared and was validated by external dataset containing known HSP90 inhibitors. This validated model was then used to virtually screen commercial databases, selected hits of which were bought and sent for real biological evaluation. Further as an alternative method, pharmacophores were generated using crystal structure conformations of ligands in HSP90 complexes (1uyi and 2bz5) and where used for virtual screening. Both cases yielded several hits containing novel scaffolds, particularly compound KHSP8 showed an IC(50) value of 0.902 μM in case of colon cancer (HT29), which is comparable to doxorubicin (0.828 μM). These compounds were being now used as leads for constructing small molecular libraries to get compounds with favourable pharmacokinetics and drug like properties. 相似文献
39.
Woo HM Lee YS Roh EJ Seo SH Song CM Chung HJ Pae AN Shin KJ 《Bioorganic & medicinal chemistry letters》2011,21(19):5910-5915
To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 4-piperidinecarboxylate and 4-piperidinecyanide derivatives were prepared and evaluated for in vitro and in vivo activity against α(1G) calcium channel. Among them, several compounds showed good T-type calcium channel inhibitory activity and minimal off-target activity over hERG channel (% inhibition at 10 μM=61.85-71.99, hERG channel IC(50)=1.57 ± 0.14-4.98 ± 0.36 μM). Selected compound 31a was evaluated on SNL model of neuropathic pain and showed inhibitory effect on mechanical allodynia. 相似文献
40.
Kaija Goodman Julio Paez-Valencia Janice Pennington Annika Sonntag Xinxin Ding Han Nim Lee Paul G. Ahlquist Isabel Molina Marisa S. Otegui 《The Plant cell》2021,33(8):2850
Pollen wall assembly is crucial for pollen development and plant fertility. The durable biopolymer sporopollenin and the constituents of the tryphine coat are delivered to developing pollen grains by the highly coordinated secretory activity of the surrounding tapetal cells. The role of membrane trafficking in this process, however, is largely unknown. In this study, we used Arabidopsis thaliana to characterize the role of two late-acting endosomal sorting complex required for transport (ESCRT) components, ISTL1 and LIP5, in tapetal function. Plants lacking ISTL1 and LIP5 form pollen with aberrant exine patterns, leading to partial pollen lethality. We found that ISTL1 and LIP5 are required for exocytosis of plasma membrane and secreted proteins in the tapetal cells at the free microspore stage, contributing to pollen wall development and tryphine deposition. Whereas the ESCRT machinery is well known for its role in endosomal trafficking, the function of ISTL1 and LIP5 in exocytosis is not a typical ESCRT function. The istl1 lip5 double mutants also show reduced intralumenal vesicle concatenation in multivesicular endosomes in both tapetal cells and developing pollen grains as well as morphological defects in early endosomes/trans-Golgi networks, suggesting that late ESCRT components function in the early endosomal pathway and exocytosis.Endosomal sorting complex required for transport proteins ISTL1 and LIP5 are required for exocytosis of both plasma membrane and secreted proteins in tapetal cells during microspore formation. 相似文献