scholarly journals Design, Synthesis and Biological Evaluation of Diosgenin-Amino Acid Derivatives with Dual Functions of Neuroprotection and Angiogenesis

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4025 ◽  
Author(s):  
Desheng Cai ◽  
Jinchai Qi ◽  
Yuqin Yang ◽  
Wenxi Zhang ◽  
Fei Zhou ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Line ◽  
Chorioallantoic Membrane ◽  
Biological Evaluation ◽  
Amino Acid Derivatives ◽  
H9c2 Cell ◽  
Protecting Group ◽  
Neuroprotective Effects ◽  
Wide Range ◽  
Dual Functions

Diosgenin, a natural product with steroidal structure, has a wide range of clinical applications in China. It also shows great potential in the treatment of blood clots and nerve damage. To enhance the bioavailability as well as efficacy of diosgenin, eighteen diosgenin-amino acid derivatives were designed and synthesized. The neuroprotective effects of these compounds were evaluated by SH-SY5Y cell line and the biosafety was evaluated by H9c2 cell line. The results displayed that part of the derivatives’ activities (EC50 < 20 μM) were higher than positive control edaravone (EC50 = 21.60 ± 3.04 μM), among which, DG-15 (EC50 = 6.86 ± 0.69 μM) exhibited the best neuroprotection. Meanwhile, biosafety evaluation showed that DG-15 had no cytotoxicity on H9c2 cell lines. Interestingly, combined neuroprotective and cytotoxic results, part of the derivatives without their protecting group were superior to compounds with protecting group. Subsequently, Giemsa staining and DAPI (4′,6-diamidino-2-phenylindole) staining indicated that DG-15 had a protective effect on damaged SH-SY5Y cells by reducing apoptosis. Moreover, DG-15 showed a higher role in promoting angiogenesis at high concentrations (4 mg/mL) on the chorioallantoic membrane model. This finding displayed that DG-15 had dual functions of neuroprotection and angiogenesis, which provided further insight into designing agent for the application in treatment of ischemic stroke.

scholarly journals Synthesis of Novel Baicalein Amino Acid Derivatives and Biological Evaluation as Neuroprotective Agents

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3647 ◽  
Author(s):  
Xiaohui Jia ◽  
Menglu Jia ◽  
Yuqin Yang ◽  
Di Wang ◽  
Fei Zhou ◽  
...  
Keyword(s):  
Amino Acid ◽  
High Resolution Mass Spectrometry ◽  
Neuroprotective Effect ◽  
Biological Evaluation ◽  
Neuroprotective Activity ◽  
Amino Acid Derivatives ◽  
H9c2 Cell ◽  
Butyl Hydroperoxide ◽  
Tert Butyl ◽  
Tert Butyl Hydroperoxide

Baicalein, a famously effective component of the traditional Chinese medicine Rhizoma Huang Qin (Scutellaria altissima L.), has been proved to have potent neuroprotection and anti-platelet aggregation effects with few side effects. Meanwhile, recent studies have revealed that the introduction of amino acid to baicalein could improve its neuroprotective activity. In the present study, a series of novel baicalein amino acid derivatives were designed, synthesized, and screened for their neuroprotective effect against tert-butyl, hydroperoxide-induced, SH-SY5Y neurotoxicity cells and toxicity on the normal H9C2 cell line by standard methylthiazol tetrazolium (MTT) assay. In addition, all of the newly synthesized compounds were characterized by 1H-NMR, 13C-NMR, and high resolution mass spectrometry (HR-MS). The results showed that most of the compounds provided more potent neuroprotection than baicalein, and were equivalent to the positive drug edaravin. They showed no obvious cytotoxicity on normal H9C2 cells. Notably, the most active compound 8 displayed the highest protective effect (50% effective concentration (EC50) = 4.31 μM) against tert-butyl, hydroperoxide-induced, SH-SY5Y neurotoxicity cells, which was much better than the baicalein (EC50 = 24.77 μM) and edaravin (EC50 = 5.62 μM). Further research on the chick chorioallantoic membrane (CAM) model indicated that compound 8 could significantly increase angiogenesis, which might promote neurovascular proliferation. The detection of apoptosis analysis showed that compound 8 could dramatically alleviate morphological manifestations of cell damage. Moreover, the benzyloxycarbonyl (cbz)-protected baicalein amino acid derivatives showed better neuroprotective activity than the t-Butyloxy carbonyl (boc)-protected derivatives.

scholarly journals Synthesis and Preliminary Biological Evaluation of 1,3,5-Triazine Amino Acid Derivatives to Study Their MAO Inhibitors

Molecules ◽  
2015 ◽  
Vol 20 (9) ◽  
pp. 15976-15988 ◽  
Author(s):  
Sherine Khattab ◽  
Hosam Khalil ◽  
Adnan Bekhit ◽  
Mohamed El-Rahman ◽  
Ayman El-Faham ◽  
...  
Keyword(s):  
Amino Acid ◽  
Biological Evaluation ◽  
Amino Acid Derivatives ◽  
Mao Inhibitors

scholarly journals Synthesis and Biological Evaluation of Novel Phenylpropenoyl-amino Acid Derivatives

2019 ◽  
Vol 39 (7) ◽  
pp. 1953
Author(s):  
Sufan Gao ◽  
Yanchun Zhang ◽  
Jiaming Li ◽  
Bin Zhang ◽  
Yu Yang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Biological Evaluation ◽  
Amino Acid Derivatives ◽  
Synthesis And Biological Evaluation

scholarly journals Biomimetic enantioselective synthesis of β,β-difluoro-α-amino acid derivatives

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Qiupeng Peng ◽  
Bingjia Yan ◽  
Fangyi Li ◽  
Ming Lang ◽  
Bei Zhang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Structural Diversity ◽  
Enantioselective Synthesis ◽  
Amino Acid Derivatives ◽  
Proton Shift ◽  
Wide Range ◽  
Fluorine Compounds ◽  
Optically Pure ◽  
High Stereoselectivity ◽  
High Application

AbstractAlthough utilization of fluorine compounds has a long history, synthesis of chiral fluorinated amino acid derivatives with structural diversity and high stereoselectivity is still very appealing and challenging. Here, we report a biomimetic study of enantioselective [1,3]-proton shift of β,β-difluoro-α-imine amides catalyzed by chiral quinine derivatives. A wide range of corresponding β,β-difluoro-α-amino amides were achieved in good yields with high enantioselectivities. The optically pure β,β-difluoro-α-amino acid derivatives were further obtained, which have high application values in the synthesis of fluoro peptides, fluoro amino alcohols and other valuable fluorine-containing molecules.

Synthesis and Biological Evaluation of SeCF3‐Substituted α‐Amino Acid Derivatives

ChemMedChem ◽  
2021 ◽  
Author(s):  
Zhou-Zhou Han ◽  
Tao Dong ◽  
Xiao-Xia Ming ◽  
Fu Kuang ◽  
Cheng-Pan Zhang
Keyword(s):  
Amino Acid ◽  
Biological Evaluation ◽  
Amino Acid Derivatives ◽  
Synthesis And Biological Evaluation

scholarly journals Effects of Schiff base aromatic amino acid derivatives on antioxidant and immune system disturbances in a rat model of aflatoxin B1 induced experimental mycotoxicosis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1413
Author(s):  
Margarita Malakyan ◽  
Violeta Ayvazyan ◽  
Gayane Manukyan ◽  
Laura Hovsepyan ◽  
Elina Arakelova ◽  
...  
Keyword(s):  
Schiff Base ◽  
Amino Acid ◽  
Rat Model ◽  
Cell Damage ◽  
Malonic Dialdehyde ◽  
Water Soluble ◽  
Amino Acid Derivatives ◽  
Antioxidant Systems ◽  
Wide Range ◽  
Late Apoptosis

Background:Alflatoxin B1 (AFB1) is the most hepatotoxic and hepatocarcinogenic of the aflatoxins and occurs as a contaminant in a variety of foods. The toxicity of AFB1 has been shown to be associated with a wide range of pathological events, such as enhanced apoptosis and oxidative events. Currently there is no treatment for mycotoxin exposure. The aim of this study was to evaluate the potential ability of picolinyl-L-phenylalaninate (PLP), picolinyl-L-tryptophanate (PLT), and nicotinyl-L-tryptophanate (NLT) Schiff base amino acid derivatives to act against damaging effects of AFB1 using a rat model of mycotoxicosis. For this purpose, a range of markers of immune and antioxidant systems in liver and blood plasma samples, as well as the apoptotic rate in neutrophils and monocytes was assessed.Methods:Mongrel white pubescent rats (with 180-200g b/w) were used in all experiments. Concentration of the markers of immune and antioxidant systems was measured in plasma by ELISA, using commercially available kits according to manufacturers’ instructions. The rate of apoptosis in neutrophils and monocytes was analyzed by flow cytometry.Results:AFB1 induced mycotoxicosis caused significant elevation of malonic dialdehyde contents (plasma and liver: p = 0.0001 compared with untreated rats), the levels of superoxide dismutase (p=0.005), total non-enzymatic water-soluble antioxidants (p = 0.0001), and terminal complement complex (p = 0.021). Moreover, the increased rates of early and late apoptosis in neutrophils and monocytes were observed as well. Treatment with PLP, PLT and NLT were shown to mitigate these effects, though to a different extent.Conclusions:The results obtained in this study clearly demonstrated that chronic AFB1 exposure induced oxidative cell damage, immunosuppression and apoptosis of circulating immune cells. The oral administration of Schiff base cyclic amino acid derivatives was capable of minimizing the detrimental effects of mycotoxicosis by possessing multi-mechanistic effects that target AFB1-induced pathological events.

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