摘要：
<jats:p>A novel organoantimony complex of 6‐cyclohexyl‐6,7‐dihydrodibenzo[<jats:italic>c,f</jats:italic>] [<jats:italic>1,5</jats:italic>]azastibocin‐12(5H)‐yl nitrate (<jats:bold>2</jats:bold>) was synthesized and systematically characterized by techniques such as NMR spectra, TG‐DSC, and X‐ray diffraction. It was found that the complex <jats:bold>2</jats:bold> exhibits relatively strong Lewis acidity (3.3 < <jats:italic>Ho</jats:italic> ≤ 4.8) and could be employed as a water tolerant Lewis acid catalyst for the synthesis of synthetically valuable benzimidazole derivatives starting from aldehydes and arylenediamines. This catalytic system shows excellent tolerance toward a wide variety of functional groups, such as methyl, methoxyl, fluoro, chloro, bromo, nitro, cyan, trifluoromethyl, 1‐naphthaldehyde, furfural and <jats:italic>n</jats:italic>‐butyl, together with facile reusability in 5 times scale enlarged synthesis.</jats:p>
作者机构：
[Xue Z.; Yan Z.; Bian Q.; Hou Y.; Liu Y.] School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China;[Chen Y.] School of Basic Medicine, Guizhou University of Chinese Medicine, Guiyang, 550025, China;[Yu R.] School of Graduate Students, Hunan University of Traditional Chinese Medicine, Changsha, 410208, China;School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China;[Chen C.] School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China<&wdkj&>School of Basic Medicine, Guizhou University of Chinese Medicine, Guiyang, 550025, China
通讯机构：
[Jiaxu Chen] S;School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China<&wdkj&>School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China
通讯机构：
[Chen, Y ; Yin, SF ; Qiu, RH] H;Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China.;Hunan Univ Chinese Med, Sch Med, Changsha 410208, Hunan, Peoples R China.
摘要：
A series of organoantimony(iii) halide complexes with a tetrahydrodibenzo[c,f][1,5]azastibocine framework were synthesized and employed as water tolerant Lewis acid catalysts. The results of a systematic structure-activity relationship study demonstrated that the strength of N -> Sb donor-acceptor interaction could be synergistically modulated by tuning the properties of the nitrogen substituents and halogen atoms adjacent to the central antimony atom, and consequently resulted in distinct catalytic performances towards organic reactions such as Mannich, cross-condensation, cyclization-aromatization and epoxide aminolysis reaction. The fluorinated organoantimony(iii) derivatives were found to be more active than those of the chlorinated, brominated and iodinated analogues, owing to the use of an Sb-F moiety as a hydrogen bond acceptor. By comparison, the compound 6-cyclohexyl-12-fluoro-5,6,7,12-tetrahydrodibenzo[c,f][1,5] azastibocine (1d) is found to exhibit the highest catalytic activity, together with facile reusability in scale enlarged synthesis.
期刊：
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY,2019年316(6):G774-G784 ISSN：0193-1857
通讯作者：
Li, YC
作者机构：
[Adhikari, Sarbani; Pekow, Joel; Rubin, David T.; Zhou, Min; He, Lei; Du, Jie; Chen, Yinyin; Liu, Chunyan; Li, Yan Chun] Univ Chicago, Dept Med, Div Biol Sci, Chicago, IL 60637 USA.;[Du, Jie] Shanxi Med Univ, Inst Biomed Res, Taiyuan, Shanxi, Peoples R China.;[Chen, Yinyin] Hunan Normal Univ, Hunan Prov Peoples Hosp, Dept Nephrol, Changsha, Hunan, Peoples R China.;[Liu, Chunyan] Hunan Univ Chinese Med, Dept Pathol, Changsha, Hunan, Peoples R China.;[Zhou, Min] Shanghai Jiao Tong Univ, Xinhua Hosp, Div Gastroenterol, Sch Med, Shanghai, Peoples R China.
通讯机构：
[Li, YC ] U;Univ Chicago, Dept Med, 900 E 57th St,KCBD 9110, Chicago, IL 60637 USA.
关键词：
JAK;STAT;T17;colitis;mucosal inflammation;renin-angiotensin system
摘要：
Previous studies suggest that the renin-angiotensin system (RAS) is a pathogenic factor for colitis. The goal of this study was to elucidate the molecular mechanism whereby angiotensin II (ANG II) promotes colonic inflammation. We found that renin was highly induced in colonic biopsies from patients with ulcerative colitis or Crohn's disease, and colonic renin and ANG II levels were markedly increased in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model, indicating that the colonic RAS is activated in colitis. Renin transgenic (RenTg) mice exhibited increased phosphorylation in Janus kinase-2 (JAK2) and signal transducer and activator of transcription1/3 (STAT1/3) within colonic mucosa at baseline and following TNBS induction, suggesting that ANG II promotes colonic inflammation via the JAK2/STAT1/3 pathway. Treatment with pan-JAK inhibitor tofacitinib blocked JAK2 and STAT1/3 phosphorylation, attenuated T helper (TH)1 and TH17 responses, alleviated colitis, and prevented death of RenTg mice in TNBS model. ANG II stimulated JAK2/STAT1/3 phosphorylation in both Jurkat T lymphocytes and HCT116 epithelial cells. In vitro polarization assays demonstrated that ANG II directly promoted TH17 polarization, but not TH1 polarization, via JAK2/STAT1/3. ANG II stimulation of transforming growth factor-beta1 (TGFbeta1), IL-6, myosin light chain kinase, and p53 upregulated modulator of apoptosis in HCT116 cells was also mediated by JAK2/STAT1/3. These observations suggest that ANG II promotes TH17 polarization directly as well as indirectly by inducing production of TH17-polarizing cytokines (e.g., TGFbeta1 and IL-6) from colonic epithelial cells, both via the JAK2/STAT pathway. Therefore, colonic RAS promotes colonic inflammation, at least in part, by stimulating TH17 activation. NEW & NOTEWORTHY This study demonstrates that the local renin-angiotensin system in the colon is activated in colitis development, which promotes mucosal T helper cell activation through the JAK2/STAT pathway. These observations provide molecular evidence that the renin-angiotensin system is a pathogenic factor for the development of inflammatory bowel diseases.
摘要：
The relationship between chemical structure and in vitro cytotoxic activities of a series of azastibocine-framework organoantimony(III) halide complexes against cancerous (HepG2, MDA-MB-231, MCF-7 and HeLa) and nonmalignant (HEK-293) cell lines was studied for the first time. A positive correlation between cytotoxic activity and the length of N-->Sb coordinate bond on azastibocine framework of same nitrogen substituent was observed. By comparison, the organoantimony(III) complex 6-cyclohexyl-12-fluoro-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (C4) exhibited the highest selectivity index, giving a IC50(nonmalignant)/IC50(cancerous) ratio of up to 8.33. The results of cell cycle analysis indicated that the inhibitory effect of C4 on the cellular viability was caused by cell cycle arrest mainly at the S phase. The necrosis induced by C4 was confirmed by the Trypan blue dye exclusion test and the increase of lactic dehydrogenase (LDH) released in the culture medium. Furthermore, evaluation of the levels of intracellular reactive oxygen species (ROS) in MDA-MB-231cells, by quantifying the relative fluorescence units (RFU) using spectrofluorometer, indicated that cytotoxic activity of C4 is dependent on the production of ROS. This work established the correlation between cytotoxic activity and N-->Sb inter-coordination, a finding that provided theoretical and experimental basis for in-depth design of antimony-based organometallic complexes as potential anticancer agents.
摘要：
<jats:title>Abstract</jats:title><jats:p>A convenient synthetic approach for the synthesis of α‐oxo‐acetamidines via copper‐catalyzed C(sp<jats:sup>3</jats:sup>)‐H amidination has been developed.This approach allows the direct amidination of three C(sp<jats:sup>3</jats:sup>)‐H bonds without cyclization.Methyl ketones and primary and secondary amines are tolerant and afford the corresponding products in moderate to good yields. Furthermore, this protocol is also applicable to the synthesis of unsymmetrical α‐oxo‐acetamidines via one‐pot, multicomponent reactions (MCRs).</jats:p>
摘要：
<jats:title>Abstract</jats:title><jats:p>An chelation‐assisted oxidative C(<jats:italic>sp</jats:italic><jats:sup>3</jats:sup>)−H/N−H cross coupling of hydrocarbons with P(O)−NH compounds using copper acetate as catalyst is described. The results of kinetic experiments, mechanistic studies and DFT calculations demonstrate the importance of acetic acid coproduct as an additive for promoting the formation of intermediate bis((diphenylphosphoryl)(quinolin‐8‐yl)amino)copper (<jats:bold>6</jats:bold>), and consequently accelerating the construction of C(<jats:italic>sp</jats:italic><jats:sup>3</jats:sup>)−N bond. The reaction proceeded efficiently with a wide array of hydrocarbons and P(O)−NH compounds, and the rate acceleration induced by the acetic acid coproduct have been repeatedly proven. Furthermore, the efficiency of small‐scale reaction could be retained upon gram‐scale synthesis in a continuous manner.</jats:p><jats:p><jats:boxed-text content-type="graphic" position="anchor"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" mimetype="image/png" position="anchor" specific-use="enlarged-web-image" xlink:href="graphic/adsc201801694-toc-0001-m.png"><jats:alt-text>magnified image</jats:alt-text></jats:graphic></jats:boxed-text>
</jats:p>
通讯机构：
[Chen, Y ; Yin, SF ] H;Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China.;Hunan Univ Chinese Med, Sch Basic Med, Changsha 410208, Hunan, Peoples R China.
关键词：
Csp3-H bond activation;oxidative dehydrogenation;copper-catalyzed;esterification
摘要：
<jats:title>Abstract</jats:title><jats:p>Copper‐catalyzed cross‐dehydrogenative esterification of readily available <jats:italic>N</jats:italic>‐heteroaryl methanes with acids has been realized in good to excellent yields of target products. Through simple regulation of acid loading, it is possible to achieve mono‐ or di‐esterification of the methyl group with high chemoselectivity. The protocol is suitable for a wide scope of substrates and exhibits high step efficiency and atom economy. It is envisaged that this radical‐promoted one‐pot dual functionalization of C(sp<jats:sup>3</jats:sup>)−H bond is a general and facile strategy that would enrich the applications of <jats:italic>N</jats:italic>‐heteroaryl methanes.</jats:p>
作者机构：
[Yongping Liu; Yi Chen; Kun Yu; Jian Lei; Chak-Tong Au; Shuang-Feng Yin] Medical College,Hunan University of Chinese Medicine;[Yongping Liu; Yi Chen; Kun Yu; Jian Lei; Chak-Tong Au; Shuang-Feng Yin] State Key Laboratory of Chemo/Biosensing and Chemometrics,College of Chemistry and Chemical Engineering,Provincial Hunan Key Laboratory for Cost-effective Utilization of Fossil Fuel Aimed at Reducing Carbon-dioxide Emissions,Hunan University;[Yongping Liu; Yi Chen; Kun Yu; Jian Lei; Chak-Tong Au; Shuang-Feng Yin] College of Chemistry and Chemical Engineering,Hunan Institute of Engineering
会议名称：
2016年国际生理学学术大会
会议时间：
2016-09-25
会议地点：
中国北京
摘要：
Based on the interaction mode between compounds and DNA,this study aimed to investigate the cytotoxic and apoptotic activity of two heterocyclic organobismuth compounds([O（CH2C6H4）2]BiCl: C1 and [
摘要：
8-bromo-7-methoxychrysin (BrMC), a novel chrysin analog, was reported to have anti-cancer activities. The aim of the present study was to investigate the molecular mechanism of 8-bromo-7-methoxychrysin (BrMC)-induced apoptosis via the Akt/forkhead box O3a (FOXO3a) pathway in cisplatin (DDP)sensitive and resistant ovarian cancer cells. The human ovarian cancer cell lines A2780 and A2780/DDP were cultured in vitro. Various molecular techniques were used to assess the expression of FOXO3a and B cell lymphoma 2 (Bcl-2)interacting mediator of cell death (Bim) in cisplatin-sensitive and resistant ovarian cancer cells. Different concentrations of BrMC induced apoptosis in cisplatin-sensitive and resistant ovarian cancer cells. BrMC-induced apoptotic cell death occurred mainly by the activation of Akt, which was accompanied by the overexpression of transcription factor FOXO3a, with a concomitant increase in the expression levels of Bim. Silencing Bim expression by using small interfering RNA, attenuated the induction of apoptosis by BrMC treatment. The results indicated that BrMC-induced apoptosis in cisplatin-sensitive and resistant ovarian cancer cells may occur via the regulation of Akt/FOXO3a, leading to Bim transcription.
