关键词：
Alkyl amines;Alkyl radicals;C(sp3)−N bond cleavage;Deaminative functionalization;Katritzky salts
摘要：
The amino group is one of the most prevalent functional groups present in a wide range of organic molecules, which has been widely applied in various organic synthesis and pharmaceuticals. Alkyl amines could be converted in a single step into Katritzky salts which could serve as alkyl radical precursors to construct C−C bonds and C−X bonds via C(sp3)−N cleavage. This deaminative functionalization could be carried out under transition-metal catalysis, photocatalysis, carbene catalysis or promoted by base. In this paper, recent developments in the deaminative functionalization of alkyl amines were covered. This review was categorized into four parts according to the nature of the bond formation. Some representative examples and corresponding reaction mechanisms were also summarized.
关键词：
cycloketone oximes;cyanoalkyl radical;radical cross-coupling;C−C bond cleavage
摘要：
Recent years have witnessed a renaissance of radical cross-coupling of cycloketone oximes which served as active cyanoalkyl radical via ring fragmentation in various transformations. It provided an efficient and practical strategy to introduce cyanoalkyl groups into organic compounds without using toxic cyanide sources. In this review, a comprehensive overview of recent advances in the field of redox-active cycloketone oximes-based cross-couplings were covered. This review was categorized into two broad parts: non-photocatalyzed and photocatalyzed cross-couplings according to the reaction conditions. Moreover, the two broad parts were further divided into several sub-sections depending on the nature of the bond formation. Some representative examples along with reaction mechanisms were also discussed. 1. Introduction 2. Transition-Metal Catalyzed Cross-Coupling Reactions 2.1. C(sp(3))-C(sp(3)) Bond Formation 2.2. C(sp(3))-C(sp(2)) Bond Formation 2.3. C(sp(3))-C(sp) Bond Formation 2.4. C(sp(3)) N/O/S/Se Bond Formation 3. Microwave-Promoted Cross-Coupling Reactions 4. Gallic acid-Promoted Cross-Coupling Reactions 5. DMAc/B-2(OH)(4) or DMAc-Promoted Cross-Coupling Reactions 6. Photocatalyzed Cross-Couplings Reactions 6.1. Reductive Activation Modes of Cycloketone Oximes 6.2. Oxidative Activation Modes of Cycloketone Oximes 7. Conclusion
摘要：
Genistein is a phytoestrogen compound which possesses multiple biological activities such as anti-cancer, while its application is limited by poor pharmacokinetic properties. Structural modification is an effective approach to get genistein derivatives with better activities and approved pharmacokinetic properties. Based on previous research work, we synthesized two series of genistein derivatives bearing halogen substituents, and evaluated their inhibitory effects on the cancer cell lines MCF-7, MDA-MB-231, and MDA-MB-435. Among these derivatives, compound XI displayed the best inhibitory activity against MCF-7, MDA-MB-231 and MDA-MB-435 cell lines in vitro, which is worth further studies.
摘要：
An efficient and metal-free coupling reaction has been developed that affords acetamides from the corresponding aryl amines and acetonitrile. This method tolerates a wide range of functional groups and is selective toward aryl amines. Preliminary mechanistic studies were conducted.
摘要：
A series of chrysin amino acid derivatives were synthesized to evaluate for their antiproliferative activities against several cancer cell lines. Among the compounds tested, N-(2-((5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy)octanoyl)-L-leucine methyl ester(5d) presented a good anti-proliferative activity in MDA-MB-231 and MCF-7 cells. Flow cytometry analysis showed that 5d induced apoptosis and prolonged cell cycle progression in MDA-MB-231 and MCF-7 cells. Western blot analysis showed that 5d significantly inhibited Akt phosphorylation (Ser473) in MDA-MB-231 and MCF-7 cells. In addition, 5d treatment markedly downregulated Bcl-2 and upregulated Bax in a dose-dependent manner. In vitro caspase activation assay showed that 5d induced apoptosis of MDA-MB-231 cells by enhancing caspase 3/7 activity. The regulatory effect of 5d on apoptosis of MDA-MB-231 and MCF-7 cells may be induced by mitochondrial apoptosis pathway. This study is of great significance for designing and developing more effective chrysin amino acid derivatives. [GRAPHICS] .
摘要：
Chrysin is a natural product of a flavonoid compound. Chemically, chrysin consists of two phenyl rings (A and B) and a heterocyclic ring (C). Biologically, chrysin exerts many different physiological activities. In recent years, with the in-depth development for more active drugs, the synthesis and biological activities of chrysin derivatives have been well studied. Besides, structure-activity relationship of chrysin revealed that the chemical construction meets the critical chemical structural necessities of flavonoids for numerous pharmacological activities. It is generally believed that modified chrysin could be more potent than unmodified chrysin. Different modification in the rings of chrysin could possess various degrees of biological activities. This review aims to summarize the mechanism for the activities of chrysin and its derivatives in different rings. We also explored the relationship between biological function and structure-activity of substituted chrysin derivatives with different functional groups. The influence of chrysin derivatives on the proliferation and apoptosis of cancer cells is also investigated. Development of novel drugs based on the biological functions of chrysin could better improve clinical outcomes of affected population, especially for tumor patients and diabetic patients.
作者机构：
Institute of Pharmacy & Pharmacology,Hunan Province Cooperative innovation Center for Molecular Target New Druge Study,University of South China, Hengyang, 421101;Institute of Chemistry & Chemical Engineering,University of South China, Hengyang, 421101;[刘鼎; 成林; 郭玉; 刘运美] Institute of Pharmacy & Pharmacology,Hunan Province Cooperative innovation Center for Molecular Target New Druge Study,University of South China, Hengyang, 421101;[何军] Institute of Chemistry & Chemical Engineering,University of South China, Hengyang, 421101
摘要：
To improve the clinical effect of scutellarin by extending the action time in vivo, scutellarin loaded polymeric micelles were developed by D-alpha tocopherol polyethylene glycol 1000 succinate (Scu/TPGS). Scu/TPGS were prepared using film solvent diffusion methods and characterized on the basis of their particle size, zeta potential, and drug encapsulation efficiency. Dynamic dialysis was used to study the release behavior of the polymeric micelles in vitro. Its pharmacokinetic characteristics and antithrombotic efficacy were studied by intravenous injection in rats. The results showed that Scu/TPGS were spherical, 20.09 +/- 2.62 nm in size and a slow release in vitro. The pharmacokinetic parameter T-1/2 of Scu/TPGS was 762.12 +/- 46.56 min compared with commercial injection of 59.30 +/- 10.67 min (p < 0.05). At the 1 mg/kg dose, the thrombolysis effect of micellar group was stronger than that of the commercial group (p < 0.05). In conclusion, TPGS polymer micelles provided a valid strategy in chemotherapy for cerebrovascular diseases with poor water solubility and poor lipid solubility drugs such as scutellarin.
摘要：
Here, we report a new approach of on-resin peptide ligation using C-terminal benzyl ester as the stabilized precursor of thioester, which enables both N-terminal elongation and C-terminal peptide ligation on a Rink Amide resin. On-resin native chemical ligation and auxiliary-assisted peptide ligation were successfully achieved. This method is compatible to both protected and unprotected peptide fragments and has potential application in poor water-soluble peptide ligation.
通讯机构：
[Guo, Yu] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
摘要：
Genistein amino acid derivatives 4a–4d were synthesized and evaluated for their cytotoxic activities against MCF-7, Hela, MGC-803 and HCT-116 cell lines by MTT assays in vitro. The results revealed that compounds 4a–4d showed better activity than the parent compound genistein. Particularly, compound 4b displayed the most significant anticancer activity against MGC-803 with an IC50 value of 12.08 μM. In addition, the mechanisms of interaction between genistein, compounds 4a–4d and BSA were investigated via multi-spectroscopic techniques such as ultraviolet (UV) spectroscopy, fluorescence, circular dichroism (CD), and molecular docking under physiological conditions. The results suggested that endogenous fluorescence of BSA could be quenched by genistein and compounds 4a–4d via forming BSA-compound complex, which meant a static quenching mechanism was involved. The negative values of enthalpy (ΔH) and entropy (ΔS) indicated that interactions between BSA and the ligands were spontaneous, and hydrogen bonding and van der Waals interactions were involved in the BSA-compound complexion formation. The UV, synchronous and 3D fluorescence results revealed that the micro-environment of tryptophan and conformation of BSA were changed after binding to ligands. CD analysis demonstrated the variation in the secondary structure and that the α-helix content of BSA decreased. Eventually, molecular docking was executed to forecast the binding forces and binding sites between BSA and compounds 4a–4d.
作者：
Qionglin Zhou;Kai Zhang;Yu Guo;Linxi Chen;Lanfang Li
期刊：
生物化学与生物物理学报,2018年50(3):319-321 ISSN：1672-9145
通讯作者：
Chen, L.
作者机构：
[Zhou Qionglin; Zhang Kai; Guo Yu; Chen Linxi; Li Lanfang] Institute of Pharmacy and Pharmacology, University of South China, Learning Key Laboratory for Pharmacoproteomics;[Zhou Qionglin; Zhang Kai; Guo Yu; Chen Linxi; Li Lanfang] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang, 421001
通讯机构：
[Chen, L.] I
关键词：
apoptosis;APELIN
摘要：
APJ is a seven-transmembrane G protein coupled receptor. Apelin is an endogenous ligand of APJ [1]. It is well known that Apelin and APJ receptor are widely distributed in a variety of organs including the heart, brain, kidney, stomach, lung, adipose tissues, endothelium, vascular smooth muscle cells, testis, ovary, and gland, particularly in the cardiovascular system. The Apelin/APJ system plays multiple important roles in various physiological and pathological processes such as regulation of blood pressure, cardiac contractility, water homeostasis, immunity, glucose metabolism, fat metabolism, inflammation, liver fibrosis, cardiovascular development, apoptosis, revascularization, as well as cell proliferation.
