期刊：
CURRENT PHARMACEUTICAL DESIGN,2014年20(5):685-686 ISSN：1381-6128
通讯作者：
Yang, Guang-Fu
作者机构：
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P.R. China.,China;[Yang, Guang-Fu] Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P.R. China.,China
通讯机构：
Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, China
通讯机构：
[Yang, Wen-Chao] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.
摘要：
Two novel coumarin-derived fluorescent probes were designed and synthesized for the quantitative determination of biothiols, such as cysteine (Cys), glutathione (GSH) and homocysteine (Hcy). Both probes selectively and sensitively detected biothiols in vitro, and successfully sensed biothiols in vivo with low cytotoxicity, suggesting their potential application for biothiol detection.
作者机构：
[赵新筠; 陈喜] College of Chemistry and Materials Science, South-Central University for Nationalities;[杨光富] College of Chemistry, Huazhong Normal University;[湛昌国] Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky
作者机构：
[Yang, Guangfu; Wang, Pingyuan] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan, Peoples R China.;[Wang, Pingyuan; Zhang, Ao] Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 200031, Peoples R China.;[Wang, Pingyuan; Zhang, Ao] Chinese Acad Sci, Shanghai Inst Mat Med, Synthet Organ & Med Chem Lab, Shanghai 200031, Peoples R China.;[Miao, Zehong; Song, Shanshan] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China.
通讯机构：
[Yang, Guangfu] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan, Peoples R China.
摘要：
An efficient one-pot synthesis of polyhydroxyalkyl-substituted pyrroles from 1,2-cyclopropa-3-pyranones with primary amines is reported. With 10% of InBr3 as the catalyst, both aryl- and alkylamines as well as various 1,2-cyclopropa-3-pyranones are well tolerated. This method is highly appealing because of its one-pot process, mild reaction conditions, substrate simplicity, and broad substrate scope.
摘要：
Indoline-2,3-diones (isatins) and their derivatives are important heterocycles found in nature and present in numerous bioactive compounds. Very few examples related to the synthesis of 4-substituted-arylisatins have been reported before. Utilizing microwave irradiation, the synthesis of bulky 4-substituted-arylisatins via a Suzuki cross-coupling has been developed with a wide range of substrates. All the reactions proceeded smoothly and afforded moderate to excellent yields of products, which indicating that electronic effects and steric modifications have little effect on this reaction. (C) 2012 Elsevier Ltd. All rights reserved.
摘要：
Protoporphyrinogen IX oxidase (PPO; EC 1.3.3.4) is an essential enzyme catalyzing the last common step in the pathway leading to heme and chlorophyll biosynthesis. Great interest in PPO inhibitors arises from both its significance to agriculture and medicine. However, the discovery of PPO inhibitors with ultrahigh potency and selectivity is hampered due to lack of structural and mechanistic understanding about the substrate recognition, which remains a longstanding question central in porphyrin biology. To understand the mechanism, a novel binding model of protogen (protoporphyrinogen IX, the substrate) was developed through extensive computational simulations. Subsequently, amino acid residues that are critical for protogen binding identified by computational simulations were substituted by mutagenesis. Kinetic analyses of these mutants indicated that these residues were critical for protogen binding. In addition, the calculated free energies of protogen binding with these mutants correlated well with the experimental data, indicating the reasonability of the binding model. On the basis of this novel model, the fundamental mechanism of substrate recognition was investigated by performing potential of mean force (PMF) calculations, which provided an atomic level description of conformational changes and pathway intermediates. The free energy profile revealed a feedback inhibition mechanism of proto (protoporphyrin IX, the product), which was also in agreement with experimental evidence. The novel mechanistic insights obtained from this study present a new starting point for future rational design of more efficient PPO inhibitors based on the product-bound PPO structure.
通讯机构：
[Yang, Wen-Chao] C;Cent China Normal Univ, Minist Educ, Coll Chem, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
关键词：
Coumarin;Zn2+;Fluorescent probe
摘要：
A novel coumarin-derived fluorescent probe, FCP, was designed for Zn2+ quantification based on the photo-induced electron transfer (PET) mechanism. This probe selectively and sensitively detects Zn2+ in aqueous solution with wide pH range. Large fluorescence enhancement (13-fold) was observed upon the addition of Zn2+. FCP also displays excellent cell permeability in HeLa cell model and very low cytotoxicity to HEK-293 cell model. (C) 2013 Elsevier Ltd. All rights reserved.
摘要：
As widely occurring natural products, flavonoids are an important source for drug discovery, due to their structural diversity and broad-spectrum biological activity. In this work, a library of novel, thioether-substituted flavonoids with diverse heterocyclic groups was synthesized via a microwave-assisted procedure with the advantages of good yields, short times, mild conditions and ready isolation of the products. Their antiproliferative activities were evaluated against six cancer cell lines, HCCLM-7, Hela, MDA-MB-435S, SW-480, Hep-2, and MCF-7 by the MU-based assay. Compared with the positive control 5-fluorouracil, three compounds, 6a, 6b and 6j were successfully identified as the most promising candidates, due to their higher potency and broad-spectrum bioactivity with IC50 values in the range of 0.43 mu M-6.7 mu M. (C) 2013 Elsevier Masson SAS. All rights reserved.
摘要：
Functionalized 6-arylsalicylate substructures occur in a variety of pharmacologically relevant natural products and bioactive compounds. They are also broadly used as important intermediates in organic synthesis. Traditional synthetic methods have suffered from some drawbacks, such as relatively harsh reaction conditions, narrow range of substrates, and poor yields. Utilizing microwave irradiation, the synthesis of functionalized 6-arylsalicylates via a Suzuki cross-coupling has been developed with a wide range of substrates. Almost all the reactions proceeded smoothly and afforded moderate to excellent yields of products, which indicated that electronic effects and steric modifications have little effect on this reaction. (C) 2013 Elsevier Ltd. All rights reserved.
