67801-07-4Relevant academic research and scientific papers
Dual Nickel/Ruthenium Strategy for Photoinduced Decarboxylative Cross-Coupling of α,β-Unsaturated Carboxylic Acids with Cycloketone Oxime Esters
Gao, Ang,Jiang, Run-Chuang,Liu, Chuang-Chuang,Liu, Qi-Le,Lu, Xiao-Yu,Xia, Ze-Jie
supporting information, p. 8829 - 8842 (2021/06/30)
Herein, a dual nickel/ruthenium strategy is developed for photoinduced decarboxylative cross-coupling between α,β-unsaturated carboxylic acids and cycloketone oxime esters. The reaction mechanism is distinct from previous photoinduced decarboxylation of α,β-unsaturated carboxylic acids. This reaction might proceed through a nickelacyclopropane intermediate. The C(sp2)-C(sp3) bond constructed by the aforementioned reaction provides an efficient approach to obtaining various cyanoalkyl alkenes, which are synthetically valuable organic skeletons in organic and medicinal chemistry, under mild reaction conditions. The protocol tolerates many critical functional groups and provides a route for the modification of complex organic molecules.
Metal-Free Hydropyridylation of Thioester-Activated Alkenes via Electroreductive Radical Coupling
Xu, Hehuan,Liu, Jiayu,Nie, Feiyun,Zhao, Xiaowei,Jiang, Zhiyong
, p. 16204 - 16212 (2021/10/25)
An electrochemical hydropyridylation of thioester-activated alkenes with 4-cyanopyridines has been developed. The reactions experience a tandem electroreduction of both substrates on the cathode surface, protonation, and radical cross-coupling process, resulting in a variety of valuable pyridine variants, which contain a tertiary and even a quaternary carbon at the α-position of pyridines, in high yields. The employment of thioesters to the conjugated alkenes enables no requirement of catalyst and high temperature, representing a highly sustainable synthetic method.
Meta-substituted piperlongumine derivatives attenuate inflammation in both RAW264.7 macrophages and a mouse model of colitis
Gong, Zhaotang,Liu, Guoyun,Mu, Wenwen,Wang, Ziqing,Yang, Jie
, (2021/11/16)
Piperlongumine (PL) has been showed to have multiple pharmacological activities. In this study, we reported the synthesis of three series of PL derivatives, and evaluation of their anti-inflammatory effects in both lipopolysaccharide (LPS)-induced Raw264.7 macrophages and a dextran sulfate sodium (DSS)-induced mouse model of colitis. Our results presented that two meta-substituent containing derivatives 1–3 and 1–6, in which γ-butyrolactam replaced α,β-unsaturated δ-valerolactam ring of PL, displayed low cytotoxicity and effective anti-inflammatory activity. Molecular docking also showed that the meta-substituted derivative, compared with the corresponding ortho- or para-substituted derivative, had significant interactions with the amino acid residues of CD14, which was the core receptors recognizing LPS. In vitro and in vivo studies, 1–3 and 1–6 could inhibit the expression of pro-inflammatory cytokines, and the excessive production of reactive nitrogen species and reactive oxygen species. Oral administration of 100 mg/kg/day of 1–3 or 1–6 alleviated the severity of clinical symptoms of colitis in mice, and significantly reduced the colonic tissue damage to protect the colonic tissue from the DSS-induced colitis. These results suggested that meta-substituted derivatives 1–3 and 1–6 were potential anti-inflammatory agents, which may lead to future pharmaceutical development.
Design, Synthesis, and Anticancer Activity of Cinnamoylated Barbituric Acid Derivatives
Li, Peng-Xiao,Liu, Guo-Yun,Liu, Ren-Min,Liu, Yue,Mu, Wen-Wen,Sun, Ya-Lei,Yang, Jie
, (2022/01/13)
This work deals with the design and synthesis of 18 barbituric acid derivatives bearing 1,3-dimethylbarbituric acid and cinnamic acid scaffolds to find potent anticancer agents. The target molecules were obtained through Knoevenagel condensation and acylation reaction. The cytotoxicity was assessed by the MTT assay. Flowcytometry was performed to determine the cell cycle arrest, apoptosis, ROS levels and the loss of MMP. The ratios of GSH/GSSG and the MDA levels were determined by using UV spectrophotometry. The results revealed that introducing substitutions (CF3, OCF3, F) on the meta- of the benzyl ring of barbituric acid derivatives led to a considerable increase in the antiproliferative activities compared with that of corresponding ortho- and para-substituted barbituric acid derivatives. Mechanism investigation implied that the 1c could increase the ROS and MDA level, decrease the ratio of GSH/GSSG and MMP, and lead to cell cycle arrest. Further research is needed for structural optimization to enhance hydrophilicity, thereby improve the biological activity of these compounds.
Piperlongumine analogs promote A549 cell apoptosis through enhancing ROS generation
Li, Peng-Xiao,Li, Yan-Mo,Liu, Guo-Yun,Liu, Ren-Min,Mu, Wen-Wen,Sun, Ai-Ling,Sun, Ya-Lei,Yang, Jie
, (2021/06/11)
Chemotherapeutic agents, which contain the Michael acceptor, are potent anticancer molecules by promoting intracellular reactive oxygen species (ROS) generation. In this study, we synthesized a panel of PL (piperlongumine) analogs with chlorine attaching at C2 and an electronwithdrawing/electron-donating group attaching to the aromatic ring. The results displayed that the strong electrophilicity group at the C2–C3 double bond of PL analogs plays an important role in the cytotoxicity whereas the electric effect of substituents, which attached to the aromatic ring, partly contributed to the anticancer activity. Moreover, the protein containing sulfydryl or seleno, such as TrxR, could be irreversibly inhibited by the C2–C3 double bond of PL analogs, and boost intracellular ROS generation. Then, the ROS accumulation could disrupt the redox balance, induce lipid peroxidation, lead to the loss of MMP (Mitochondrial Membrane Potential), and ultimately result in cell cycle arrest and A549 cell line death. In conclusion, PL analogs could induce in vitro cancer apoptosis through the inhibition of TrxR and ROS accumulation.
Discovery of 3-cinnamamido-n-substituted benzamides as potential antimalarial agents
Futamura, Yushi,Ishiyama, Aki,Iwatsuki, Masato,Liu, Haicheng,Osada, Hiroyuki,Shi, Tao,Wu, Honghai,Zhang, Taotao,Zheng, Qunxiong,Zou, Hongbin,ōmura, Satoshi
, p. 1207 - 1218 (2022/01/06)
Background: Malaria is one of the most devastating parasitic diseases, yet the discovery of antimalarial agents remains profoundly challenging. Very few new antimalarials have been developed in the past 50 years, while the emergence of drug-resistance continues to appear. Objective: This study focuses on the discovery, design, synthesis, and antimalarial evaluation of 3- cinnamamido-N-substituted benzamides. Methods: In this study, a screening of our compound library was carried out against the multidrugsensitive Plasmodium falciparum 3D7 strain. Derivatives of the hit were designed, synthesized and tested against P. falciparum 3D7 and the in vivo antimalarial activity of the most active compounds was evaluated using the method of Peters’ 4-day suppressive test. Results: The retrieved hit compound 1 containing a 3-cinnamamido-N-substituted benzamide skeleton showed moderate antimalarial activity (IC50 = 1.20 μM) for the first time. A series of derivatives were then synthesized through a simple four-step workflow, and half of them exhibited slightly better antimalarial effect than the precursor 1 during the subsequent in vitro assays. Additionally, compounds 11, 23, 30 and 31 displayed potent activity with IC50 values of approximately 0.1 μM, and weak cytotoxicity against mammalian cells. However, in vivo antimalarial activity is not effective, which might be ascribed to the poor solubility of these compounds. Conclusion: In this study, the phenotypic screen of our compound library resulted in the first report of a 3-cinnamamide framework with antimalarial activity and 40 derivatives were then designed and synthesized. Subsequent structure-activity studies showed that compounds 11, 23, 30 and 31 exhibited the most potent and selective activity against the P. falciparum 3D7 strain with IC50 values around 0.1 μM. Our work herein sets another example of phenotypic screen-based drug discovery, leading to potentially promising candidates of novel antimalarial agents once given further optimization.
Phenanthroline functionalized polyacrylonitrile fiber with Pd(0) nanoparticles as a highly active catalyst for the Heck reaction
Xiao, Jian,Zhang, Haonan,Ejike, Anyaegbu Chima,Wang, Lu,Tao, Minli,Zhang, Wenqin
, (2021/03/03)
A series of polyacrylonitrile fibers (PANF) functionalized with nitrogen-containing ligands were prepared and then used to synthesize fiber-supported Pd(0) nanoparticle catalysts. The phenanthroline-functionalized PANF with immobilized Pd(0) nanoparticles (PANPhenF-Pd(0)) had the best catalytic activity for the Heck reaction under solvent-free conditions. The PANPhenF-Pd(0) efficiently stabilized the nanoparticles and they were well-dispersed with Pd(0) particle sizes of about 3 nm. The PANPhenF-Pd(0) structure was further characterized by a variety of instrumental methods. A probable mechanism based on the fiber's microenvironment is proposed for the Heck reaction catalyzed by PANPhenF-Pd(0). The PANPhenF-Pd(0) catalyst is easily recovered from the reaction system and can be used up to six times with only a slight decrease in catalytic activity and with low Pd leaching. The PANPhenF-Pd(0) catalyst also has excellent catalytic activity for gram-scale use.
New coumarin/sulfocoumarin linked phenylacrylamides as selective transmembrane carbonic anhydrase inhibitors: Synthesis and in-vitro biological evaluation
Angeli, Andrea,Arifuddin, Mohammed,Singh, Priti,Supuran, Claudiu T.,Swain, Baijayantimala
, (2020/07/03)
Two novel series of phenylacrylamide linked coumarins and sulfocoumarins (6a-p, 8a-i, and 14a-g) were synthesized and evaluated against four physiologically relevant human carbonic anhydrases (hCAs, EC 4.2.1.1), isoforms hCA I, hCA II, hCA IX and hCA XII for their inhibitory action. All new compounds when screened for carbonic anhydrase inhibitory activity have shown selective inhibition towards the tumor associated isoforms hCA IX and XII over CA I and II, with inhibition constants in the submicromolar to low nanomolar range. Compound 6b and 14g exhibited significant inhibition with low nanomolar potency against hCA IX, whereas 6k was effective against hCA XII. Compounds 6b, 14g and 6k may be considered as lead molecules for future development of cancer therapeutics based on a novel mechanism of action.
The potential role of the 5,6-dihydropyridin-2(1: H)-one unit of piperlongumine on the anticancer activity
Li, Peng-Xiao,Liu, Guo-Yun,Liu, Yue,Mu, Wen-Wen,Yang, Jie
, p. 42128 - 42136 (2020/12/09)
Piperlongumine (PL), a potent anticancer agent from the plant long pepper (Piper longum), contains the 5,6-dihydropyridin-2(1H)-one heterocyclic scaffold and cinnamoyl unit. In this paper, we synthesized a series of PL analogs and evaluated their cytotoxicity against cancer cells for the sake of exploring which pharmacophore plays a more potent role in enhancing the anticancer activities of PL. These results illustrated that the position effect, not the electronic effect, of substituents plays a certain role in the cytotoxicity of PL and its analogs. More important, the 5,6-dihydropyridin-2(1H)-one unit, a potent pharmacophore in enhancing the antiproliferative activities of PL, could react with cysteamine and lead to ROS generation, and then bring about the occurrence of ROS-induced downstream events, followed by cell cycle arrest and apoptosis. This work suggests that introducing a lactam unit containing Michael acceptors may be a potent strategy to enhancing the anticancer activity of drugs. This journal is
Pd-Catalyzed decarboxylative cross-coupling reactions of epoxides with α,β-unsaturated carboxylic acids
Lu, Xiao-Yu,Li, Jin-Song,Wang, Shi-Qun,Zhu, Yu-Jing,Li, Yue-Ming,Yan, Lu-Yu,Li, Jia-Mei,Wang, Jin-Yu,Zhou, Hai-Pin,Ge, Xiu-Tao
supporting information, p. 11123 - 11126 (2019/09/20)
A Pd-catalyzed decarboxylative cross-coupling of α,β-unsaturated carboxylic acids with cyclic and acyclic epoxides has been developed. Both β-monosubstituted and β-disubstituted unsaturated carboxylic acids, as well as conjugated diene unsaturated carboxylic acids are suitable reaction substrates. Substituted homoallylic alcohols were obtained in moderate to good yields. The product was obtained as a mixture of diastereomers favoring the anti diastereomer of the cyclic epoxides. This work provides a method for the modification of complex organic molecules containing α,β-unsaturated carboxylic acids.
