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：
<jats:sec>
<jats:title>Background::</jats:title>
<jats:p>Icariin (ICA), one of the main effective components isolated from the traditional
Chinese herb Epimedium brevicornu Maxim., has been reported to possess extensive pharmacological
actions, including enhanced sexual function, immune regulation, anti-inflammation, and antiosteoporosis.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods::</jats:title>
<jats:p>Our study was designed to investigate the effect of ICA on cell proliferation and differentiation
and the molecular mechanism of OPG/RANKL mediated by the Estrogen Receptor (ER) in
hFOB1.19 human osteoblast cells.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results::</jats:title>
<jats:p>The experimental results show that ICA can stimulate cell proliferation and increase the activity
of Alkaline Phosphatase (ALP), Osteocalcin (BGP) and I Collagen (Col I) and a number of calcified
nodules. Furthermore, the mRNA and protein expression of OPG and RANKL and the OPG/
RANKL mRNA and protein expression ratios were upregulated by ICA. The above-mentioned results
indicated that the optimal concentration of ICA for stimulating osteogenesis was 50ng/mL. Subsequent
mechanistic studies comparing 50ng/mL ICA with an estrogen receptor antagonist demonstrated that
the effect of the upregulated expression is connected with the estrogen receptor. In conclusion, ICA
can regulate bone formation by promoting cell proliferation and differentiation and upregulating the
OPG/RANKL expression ratio by the ER in hFOB1.19 human osteoblast cells.</jats:p>
</jats:sec>
作者机构：
[Liao, Lan-Qing; Guo, Yu; Zhang, Ye; Zeng, Yao-Fu; Long, Xiao-kang; Xiao, Fang] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.;[Li, Chong] Univ South China, Nanhua Affiliated Hosp, Hengyang, Peoples R China.
通讯机构：
[Guo, Yu; Li, Chong] U;Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.;Univ South China, Nanhua Affiliated Hosp, Hengyang, Peoples R China.
关键词：
amino acid;anti-tumor;genistein
摘要：
<jats:title>Abstract</jats:title><jats:p>Thirty‐one novel genistein amino acid ester derivatives were synthesized and evaluated for their anti‐proliferative activities against HUVEC cells and five cancer cells lines (HCT‐116, HeLa, HepG‐2, MCF‐7, MGC‐803). Most of the amino acid ester derivatives exhibited more inhibitory activity than their parent compound genistein. In particular, compound <jats:bold>8 j</jats:bold> (methyl(4‐((5‐hydroxy‐3‐(4‐hydroxyphenyl)‐4‐oxo‐4H‐chromen‐7‐yl)oxy)butanoyl)tryptophanate) bearing tryptophan chain showed the most cytotoxicity against HCT‐116 cells with IC<jats:sub>50</jats:sub> value of 2.76 μM. Further mechanistic studies indicated that compound <jats:bold>8 j</jats:bold> suppressed HCT‐116 cell metastasis and induced cell apoptosis in a dose‐dependent manner. Cell cycle assay showed that compound <jats:bold>8 j</jats:bold> arrested the HCT‐116 cells to G1 phase. These studies suggested compound <jats:bold>8 j</jats:bold> might be a potential candidate for developing new anticancer drugs.</jats:p>
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.
作者机构：
[Xiao, Jie; Liu, Yunmei; Yu, Wenmei; Guo, Yu; Zhang, Qizhi; Li, Yang] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[He, Jun] Univ South China, Inst Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Liu, Mengqin] Hengyang Normal Univ, Inst Chem & Mat Sci, Hengyang 421001, Peoples R China.
通讯机构：
[Liu, Yunmei; He, Jun] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;Univ South China, Inst Chem & Chem Engn, Hengyang 421001, Peoples R China.
关键词：
Anti-tumor;Drug target;Inhibitors of protein kinases;Quinazoline derivatives;Structure-activity relationship
摘要：
Quinazoline was originally utilized as an anti-tumor treatment, and its various derivatives can be directly extracted from plants. In recent years, protein kinases (PK) have been well recognized in the development of tumor drugs. Functionally, PK serves a vital role in the apoptosis, proliferation, differentiation, migration and cell cycle of tumor cells. Due to its good physicochemical properties, quinazoline skeleton, a superior type of PK inhibitor, has been extensively used in anti-tumor drug design. An increasing number of studies on quinazoline synthesis have been reported and used by different groups to effectively develop novel derivatives. Thus, several studies have been approved for the use of quinazoline derivatives as inhibitors of other kinases, including Src and histone deacetylase. The aim of the present review was to summarize the mechanism of quinazoline compounds as PK inhibitors, their biological structure-activity relationship such as the substituted quinazoline compounds with different functional groups in the apoptotic process, and their effect on the proliferation of tumor cells. The development of novel agents based on the antitumor functions of quinazoline molecular compounds may improve the clinical outcomes of the affected population, particularly in patients with cancer.
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.
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.
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.
