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Liu S.-J.,Shijiazhuang University | Cui L.-B.,Shijiazhuang University | Xu H.-L.,Key Laboratory of Structure Based Drug Design and Discovery | Xu H.-L.,Shenyang Pharmaceutical University | And 7 more authors.
Heterocycles | Year: 2013

A series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were designed, synthesized and evaluated as dual binding site acetylcholinesterase inhibitors. The target compounds exhibited promising inhibitory activity for AChE. The structure-activity relationships were discussed and their binding conformation and simultaneous interactions mode were further clarified by the molecular docking studies. © 2013 The Japan Institute of Heterocyclic Chemistry.

Sun R.,Key Laboratory of Structure Based Drug Design and Discovery | Sun R.,Shenyang Pharmaceutical University | Song J.,Key Laboratory of Structure Based Drug Design and Discovery | Song J.,Shenyang Pharmaceutical University | And 12 more authors.
Chinese Chemical Letters | Year: 2011

The estrogen receptor is a target for therapeutic agents for hormone replacement in menopausal women, osteoporosis, reproductive cancers such as breast cancer, uterine cancer and prostate cancer. 1,4-Dihydrothieno[3′, 2′:5,6]thiopyrano[4,3-c]pyrazole-3-carboxylic amide derivatives were designed, synthesized and biological evaluated as potential estrogen receptor antagonists. © 2010 Chun Hu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Wang X.,Key Laboratory of Structure Based Drug Design and Discovery | Wang X.,Shenyang Pharmaceutical University | Sun R.,Key Laboratory of Structure Based Drug Design and Discovery | Sun R.,Shenyang Pharmaceutical University | And 12 more authors.
Medicinal Chemistry | Year: 2014

Estrogen receptors (ERs) are members of a superfamily of ligand-modulated nuclear receptors, which have been associated with an increased risk of cardiovascular diseases and breast cancer. Based on molecular docking studies, 1,4-dihydrothieno[3',2':5,6]thiopyrano[4,3-c]pyrazole-3-carboxamide derivatives as estrogen receptor inhibitors with a new scaffold, have been synthesized and tested for the antitumor activity on the ER expressing (ER dependent) human MCF-7 breast cancer cell line. According to the biological activity evaluation, compound 6a demonstrated the most potent antiproliferative activity (relative inhibitory rate: 100%). Several of these compounds exhibited moderate antitumor activity and worthy of further modification to obtain more potent anticancer candidate drugs. © 2014 Bentham Science Publishers.

Wang S.-H.,Key Laboratory of Structure Based Drug Design and Discovery | Wang Y.,Key Laboratory of Structure Based Drug Design and Discovery | Zhu Y.-Y.,Key Laboratory of Structure Based Drug Design and Discovery | Han J.,Key Laboratory of Structure Based Drug Design and Discovery | And 4 more authors.
Arkivoc | Year: 2010

Five 2-aroyl-3-aryl-5H-furo[3,2-g]chromene derivatives have been synthesized, and their structures were characterized by IR, NMR, ESI-MS and elemental analysis. The crystal structure for 2-benzoyl-3-(4-methoxyphenyl)-6,7- dihydro-5H-furo[3,2-g]chromene has been determined by single-crystal X-ray diffraction. X-ray analysis reveals that the pyran ring adopts a half-chair conformation, while the fused furo[3,2-g]chromene ring is approximately coplanar with a slight distortion. The preliminary pharmacological test showed all target compounds exhibit cytotoxicities against the U2OS-EGFP-4F12G cell line. © ARKAT USA, Inc.

Qin S.-N.,Key Laboratory of Structure Based Drug Design and Discovery | Lu W.-W.,Shenyang Pharmaceutical University | Lu W.-W.,General Hospital of Shenyang Military Command | Wang Q.,Key Laboratory of Structure Based Drug Design and Discovery | And 2 more authors.
Gaodeng Xuexiao Huaxue Xuebao/Chemical Journal of Chinese Universities | Year: 2013

One novel compound 3, 5-dimethoxy phthalimide had been isolated from Lasiosphaera fenzlii Reich. The compound exhibited definite antioxidant activity. Meanwhile it was reported that many compounds with the skeleton of phthalimide displayed many bioactivities such as anti-angiogenesis, anti-inflammatory, immune regulation and anti-tumor and so on. On the comprehensive review of above evidences, a series of N-substituted-3, 5-dimethoxy phthalimide derivatives and N-substituted-3, 5-dihydroxy phthalimide derivatives were designed and synthesized. Those compounds were synthesized by the multi-step reaction, 3, 5-dimethoxybenzoic acid was used as a starting material, and sequentially generates the phthalic anhydride and phthalimide, then reacted with a series of halogenated hydrocarbons, and stripped of methyl to obtain the target compounds. Thirty-one new compounds were synthesized, and the structures were characterized by 1H NMR, 13C NMR and MS techniques. Their anti-tumor and anti-angiogenesis activities against A549 and HUVEC cell line in vitro were tested. Some compounds showed a certain activity.

Jin Z.,Key Laboratory of Structure Based Drug Design and Discovery | Jin Z.,Shenyang Pharmaceutical University | Yang L.,Key Laboratory of Structure Based Drug Design and Discovery | Yang L.,Shenyang Pharmaceutical University | And 9 more authors.
Archives of Pharmacal Research | Year: 2010

Acetylcholinesterase (AChE) inhibitors played an important role in developing a cure for Alzheimer' s disease. In order to study on the influence of modifications at different groups and side chains on the AChE inhibitory ability and the active sites of 7H-thiazolo[3,2-b][1,2,4]triazin-7-one derivatives, fourteen 3,6-diaryl-7H-thiazolo[3,2-b][1,2,4]triazin-7-one derivatives were designed and synthesized. The study of AChE inhibitory activity was carried out using the Ellman colorimetric assay with huperzine-A as the positive control drug. Most of the target compounds exhibited more than 50% inhibition at 10 μM. Some target compounds showed strong inhibition against AChE. The molecular fields analysis and preliminary structureactivity relationships are discussed. © 2010 The Pharmaceutical Society of Korea and Springer Netherlands.

Liu J.,Shenyang Pharmaceutical University | Zhang Y.,Shenyang Pharmaceutical University | Li Q.,Shenyang Pharmaceutical University | Zhuang Q.,Shenyang Pharmaceutical University | And 5 more authors.
Molecular Medicine Reports | Year: 2014

The aim of the present study was to establish an improved method for in vitro guinea pig airway smooth muscle (ASM) cell culture and to evaluate the effect of 2-(4-amino- 3-chloro-5-trifluomethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride (SPFF), a novel β2-adrenoceptor agonist, on the release of intracellular calcium in cells. A procedure for the efficient isolation, culture, passage and characterization of the cells was described. Primary ASM cells of guinea pigs were cultured by modified tissue cultivation. The cells were identified by their morphological characteristics and immunocytochemistry. The relative inhibition of the release of intracellular calcium by drugs in the cells was measured by fluorometric quantification with fluorochrome Fura-2/AM. The results were as follows: a) The ASM cells of the guinea pigs were successfully cultured and subcultured by using our improved method and typical peak-valley characteristics were observed under the phase contrast microscope; b) data from immunocytochemical staining with specific α-smooth muscle actin (α-SMA) demonstrated that the cells were ASM cells; c) the growth characteristics and cell viability demonstrated that the cells were in good condition and were able to be applied in the follow-up studies; d) the inhibitory effect of SPFF on the release of intracellular calcium was concentration-dependent when compared with the control and e) the potential mechanisms of SPFF on the inhibition of intracellular calcium may be independent of the ryanodine receptor, but may be closely associated with the inositol 1,4,5-trisphosphate receptor.

Song X.,Shenyang Pharmaceutical University | Zhang Y.,Shenyang Pharmaceutical University | Wang H.,Shenyang Pharmaceutical University | Wen H.,Shenyang Pharmaceutical University | And 6 more authors.
Journal of Physiology and Pharmacology | Year: 2016

The objective of this study is to investigate whether the inhibition of tradinterol (SPFF) against acetylcholine (ACh)-induced proliferation is mediated by Ca2+signaling in airway smooth muscle cells (ASMCs), and whether stereoselectivity of the drug exists. Guinea pig ASMCs were primarily prepared with the method described and treated with ACh combined to SPFF isomers for 24 or 48 hours, respectively. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to determine the proliferation of the guinea pig ASMCs. Ca2+fluorescent intensity in the guinea pig ASMCs, expressed with percentage increase in fluorescence when the intensity was determined with varioskan flash or shown with percentage increase in Geo Mean (GM) measured with flow cytometry, was recorded. Images of the intensity were obtained with fluorescent microscope. 2-APB, an (inositol 1,4,5-trisphosphate receptor) IP3R blocker, and NiCl2, a store-operated channel (SOC) inhibitor, were used to investigate the mechanism of SPFF isomers regulating intracellular Ca2+via IP3R on sarcoplasmic reticulum (SR) and/or SOC on plasma membrane. (–)SPFF and (±)SPFF, treated for 48 hours, showed significant inhibition against ACh-induced proliferation. The Ca2+elevation induced by ACh was concentration-dependently suppressed by SPFF isomers. (–)SPFF is the most effective but the potency of (±)SPFF is less than that of the former and stronger than that of (+)SPFF based on the half maximal inhibitory concentration (IC50) value. No significant additive effect was observed when (–)SPFF/(±)SPFF was used alone and combined with NiCl2/2-APB. As far as (+)SPFF is concerned, no similar phenomenon was observed. (–)SPFF and (±)SPFF but (+)SPFF showed significant inhibition against the percentage increase in fluorescence induced by CaCl2. It is likely that the influence of IP3RSOC-mediated Ca2+signaling in ASMCs helps (–)SPFF and (±)SPFF contribute to the suppression of ASMCs proliferation. Stereoselectivity of SPFF isomers may lead to different levels of suppression of ACh-induced intracellular Ca2+and ASMCs proliferation. Moreover, cell cycle analysis with flow cytometry was applied to the evaluation of the action in human ASMCs in order to further confirm the anti-proliferative effect of the drugs. It was found that (–)SPFF, (±)SPFF but (+)SPFF suppressed the elevated rate of cell population in Phase S over all the cells stimulated with ACh, when SPFF and its isomers were individually exposed to the cells for 72 hours. These results that demonstrate the different stereoselective activities of SPFF are in consistent with those obtained from the guinea pig ASMCs. © 2016, Polish Physiological Society. All rights reserved.

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