期刊：
European Journal of Medicinal Chemistry,2020年189:112028 ISSN：0223-5234
通讯作者：
Wang, LingLi;Zhou, W
作者机构：
[Zhou, Li] Hunan Agr Univ, Coll Sci, Furong Rd, Changsha 410128, Peoples R China.;[Chen, Wenming] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Pharmaceut, Prod Ctr, 95 Shaoshan Rd, Changsha 41007, Hunan, Peoples R China.;[Wang, LingLi; Zhou, Wen; Hu, Jiliang; Cao, Chenyang; Ye, Wenchong] Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, E 232,Waihuan Rd, Guangzhou 510006, Peoples R China.;[Shi, Yonghui] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Pharm, Guangzhou 510120, Guangdong, Peoples R China.
通讯机构：
[Wang, LL; Zhou, W ] G;Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, E 232,Waihuan Rd, Guangzhou 510006, Peoples R China.
关键词：
CYP1B1;Click reaction;PROTACs;Reversal of drug resistance;alpha-Naphthoflavone-based conjugates
摘要：
Extrahepatic cytochrome P450 161 (CYP1B1), which is highly expressed in various tumors, is an attractive and potential target for cancer prevention, therapy, and reversal of drug resistance. CYP1B1 inhibition is the current predominant therapeutic paradigm to treating CYP1B1-mediated malignancy, but therapeutic effect has little success. Herein, we reported CYP1B1 degradation in place of CYP1BI inhibition for reversing drug resistance toward docetaxel in CYP1B1-overexpressing prostate cancer cell line DU145 using a PROTAC strategy. Replacing chlorine atom of a CYP1B1 selective inhibitor we found previously with ethynyl, we got the resulting alpha-naphthoflavone derivative 5 which kept strong inhibition against CYP1B1 (IC50 = 0.4 +/- 0.2 nM) and high selectivity. Coupling of 5 with thalidomide derivatives of varying chain lengths afforded conjugates 6A-D via click reaction. In vitro cell-based assay indicated that 6C was more effective in eliminating drug resistance of CYP1B1-overexpressed DU145 cells compared with other analogues. Western blotting analysis showed CYP1B1 degradation was one main reason for the reversal of drug resistance to docetaxel and the effect was obtained in a concentration-dependent manner. This work is the first attempt to overcome CYP1B1-mediated drug resistance via CYP1B1 degradation instead of CYP1B1 inhibition, which could provide a new direction toward eliminating drug resistance. (C) 2020 Elsevier Masson SAS. All rights reserved.
期刊：
NEW JOURNAL OF CHEMISTRY,2019年43(15):6010-6020 ISSN：1144-0546
通讯作者：
Zhou, Wen;Zhou, Li
作者机构：
[Fu, Kaishuo; Yuan, Sisi; Zhou, Wen; Huang, Weiping; Li, MaoLin] Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, Waihuan Rd, Guangzhou 510006, Guangdong, Peoples R China.;[Jiang, Zhilin] Puer Univ, Puer, Yunan, Peoples R China.;[Shi, Yonghui] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Pharm, Guangzhou 510120, Guangdong, Peoples R China.;[Chen, YongJun] Guangzhou Univ Chinese Med, South China Res Ctr Acupuncture & Moxibust, Med Coll Acu Moxi & Rehabil, Waihuan Rd, Guangzhou 510006, Guangdong, Peoples R China.;[Zhou, Li] Hunan Agr Univ, Coll Sci, Changsha 410128, Hunan, Peoples R China.
通讯机构：
[Zhou, Wen] G;[Zhou, Li] H;Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, Waihuan Rd, Guangzhou 510006, Guangdong, Peoples R China.;Hunan Agr Univ, Coll Sci, Changsha 410128, Hunan, Peoples R China.
作者机构：
[Zhuang, Shuxin; Peng, Zhengyu; Lu, Mi; Zhou, Litao; Lin, Daqin; Zhuang, SX] Xiamen Univ Technol, Sch Mat Sci & Engn, Key Lab Funct Mat & Applicat Fujian Prov, Xiamen 361024, Peoples R China.;[Zhou, Nan] Hunan Agr Univ, Coll Sci, Changsha 410128, Hunan, Peoples R China.;[Wu, Qihui] Quanzhou Normal Univ, Sch Chem Engn & Mat Sci, Dept Chem Mat, Quanzhou 362000, Peoples R China.
通讯机构：
[Zhuang, SX; Lu, M] X;Xiamen Univ Technol, Sch Mat Sci & Engn, Key Lab Funct Mat & Applicat Fujian Prov, Xiamen 361024, Peoples R China.
关键词：
Dye-sensitized solar cells;Hydrothermal method;Cu modification;Zinc oxide
摘要：
The Cu-modified ZnO nanoflowers as photoanode material for dye sensitized solar cells are synthesized via a cetylmethylammonium bromide-assisted hydrothermal method. The main phase of the synthesized samples well matches the wurtzite type phase of ZnO. And the pure phase of Cu begins to appear and strengthen when the modified-Cu content excesses 1 wt%, indicating that Cu element not only dope into the lattice of ZnO but also cover on its surfaces. It is found that the morphologies of the ZnO samples can be tuned by the change of the modified-Cu content, from irregular nanoplates to cross-linked multi-leveled porous nanoflowers with a various Cu concentration of 0.5 wt%, 1 wt%, 1.5 wt% and 2 wt%, which further facilitate the dye adsorption and light-scattering. The photocurrent-voltage characteristics and electrochemical impedance spectroscopy are conducted to estimate the electrochemical properties of these solar cells with different Cu modification contents. Compared to the dye-sensitized solar cells with pure ZnO electrode, all the dye-sensitized solar cells with Cu-modified ZnO photoelectrodes present higher photovoltaic performance. The introduction of Cu into ZnO significantly enhances electron transport and retards charge recombination in the ZnO-dye interfaces, which induce the 84% improvement of short-circuit current density and 1.6 times enhancement of the power conversion efficiency for the dye-sensitized solar cells with 1.5 wt% Cu-modified ZnO photoelectrodes. (c) 2018 Elsevier Ltd. All rights reserved.
期刊：
ACS Energy Letters,2018年3(9):2159-2166 ISSN：2380-8195
通讯作者：
Prezhdo, Oleg, V;Akimov, Alexey, V
作者机构：
[Li, Wei] Hunan Agr Univ, Coll Sci, Changsha 410128, Hunan, Peoples R China.;[Zhou, Liujiang] Los Alamos Natl Lab, Los Alamos, NM 87545 USA.;[Prezhdo, Oleg, V] Univ Southern Calif, Dept Chem, Los Angeles, CA 90089 USA.;[Akimov, Alexey, V] Univ Buffalo State Univ New York, Dept Chem, Buffalo, NY 14260 USA.
通讯机构：
[Prezhdo, Oleg, V; Akimov, Alexey, V] U;Univ Southern Calif, Dept Chem, Los Angeles, CA 90089 USA.;Univ Buffalo State Univ New York, Dept Chem, Buffalo, NY 14260 USA.
摘要：
Carbohydrates and their conjugates play important roles in many biological processes including fertilization, differentiation, development, immune response, and infection. Their activities are largely dependent on the properties of terminal mono- or disaccharides. Galactose, mannose, fucose, glucose, sialic acid, etc., are commonly used as powerful scaffolds installed on drug molecules for targeting specific tissues including brain, liver, and cancers, and as epitopes for enhancing the targeting of various vaccines. This review focuses on the influence of their structural variations, including changes in sugar type, substituent groups and their positions, as well as length of linker portion, on the targeting of drugs or their efficacy. Particular attention is paid to the targeting properties of mono- and disaccharides applied in drug design and discovery.
作者机构：
[Zhou, Li] Hunan Agr Univ, Coll Sci, Changsha 410128, Hunan, Peoples R China.;[Zhang, Xu] South China Agr Univ, Coll Forestry & Landscape Architecture, 483 Wushan Rd, Guangzhou 510642, Guangdong, Peoples R China.;[Zhou, Wen] Guangzhou Univ Chinese Med, Sch Chinese Meteria Med, E 232,Waihuan Rd, Guangzhou 510006, Guangdong, Peoples R China.
通讯机构：
[Zhou, Wen] G;Guangzhou Univ Chinese Med, Sch Chinese Meteria Med, E 232,Waihuan Rd, Guangzhou 510006, Guangdong, Peoples R China.
关键词：
6-isomer of 5,8-O-dimethyl ether of shikonin;Ring-closing/ring-opening strategy;Bulky substituent;Semi-synthesis;Shikonin;Anticancer scaffold
摘要：
Synthesis of 6-isomer of 5,8-O-dimethyl ether of shikonin (13), a promising anticancer scaffold, always remains a huge challenge. Herein a key intermediate for 13, 2-(1-hydroxyl-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxynaphthalene (10), was obtained on the large-scale synthesis. A ring-closing/ring-opening strategy was applied to avoid the undesired reactivity posed by the side chain and racemization of the chiral centre. Incorporation of bulky substituent 4-((tertbutoxycarbonyl)amino)phenyl to hydroxyl group in the side chain redistributed electron density of naphthalene core (10), overwhelmingly favoring the generation of 13 when oxidized by cerium(IV) ammonium nitrate followed by hydrolysis. As a result, three 6-isomers (14a-14c) with very potent antitumor activity were easily synthesized. This study opened an novel avenue to selectively prepare 6-isomers of 5,8-dimethoxy1-1,4-naphthaquinones, bearing the synthetically challenging side chain such as 2-hydroxyl-5-methylpentenyl group. Graphical abstract A novel semi-synthesis of 6-isomer of 5,8-O-dimethyl ether of shikonin (13) was developed in a threestep rounte using a ring-closing/ring-opening strategy and a bulky substituent-mediated oxidative demethylation one.
摘要：
The problem of land is the focus of China’s reform.Under the background of vigorously promoting rural land reform,it is necessary to explore the influencing factors of rural farmland circulation and provide reference for the government toformulate policies and thus increase the income of farmers.In this paper,six representative indexes and multiple regression wasused to analyze farmland circulation.The results show that the GDP per capita,the proportion of migrant labor,the agriculturalsubsidy,the average area of contracted land for each household and the number of employees in township enterprises are impor原tant to the development of the agricultural land circulation in China
会议论文集名称：
DEStech Transactions on Environment Energy and Earth Sciences
摘要：
As cities develop in a fast pace, smart growth has become the goals for the city development of each country. In this paper, we take Atlanta as an example, then we build index assessment system of smart growth, which focus on economic prospection, social equity and environment sustainability (three of "E"). We choose ten typical indexes to measure three of "E" and use all-arranged polygon graphic index method to build smart growth mode. We build linear fitting functions for ten typical indexes respectively with the origin data in Atlanta from 2006 to 2014, then we get the predictable data in 2015 through the linear fitting functions. The next step is to bring this data to the mode and compute comprehensive scores with the year ranging from 2006 to 2015; besides, we compare the score in 2015 with that calculated by actual data. Then we do a significant test for them and the result indicates that the two scores are consistent. Smart growth mode we have built is effective, so we can use it to do prediction for the urban smart growth in the future.
