In Vivo/In Vitro Properties of Novel Antioxidant Peptide from Pinctada fucata

( Yongkai Ma ),( Kehui Huang ),( Yanyan Wu ) 한국미생물생명공학회(구 한국산업미생물학회) 2021 Journal of microbiology and biotechnology Vol.31 No.1

Due to the potential of antioxidants to scavenge free radicals in human body, it is important to be able to prepare antioxidant peptides that meet the industrial requirements for cosmetics and food. Here, we determined in vivo/in vitro activities of antioxidant peptide from P. fucata (PFAOP) prepared by bio-fermentation method. The antioxidant property test results showed the DPPH, hydroxyl, superoxide radical-scavenging, and cellular antioxidant activity. EC50 values of PFAOPs were 0.018 ± 0.005, 0.126 ± 0.008, 0.168 ± 0.005, and 0.105 ± 0.005 mg/ml, respectively, exhibiting higher antioxidant activities than glutathione (p < 0.05). Moreover, anti-proliferation and cytotoxicity activity results illustrated PFAOP has a potent anti-proliferative activity against HepG2, Caco-2, and MCF-7 carcinoma cells with no cytotoxicity. Moreover, the protocols we developed in this work demonstrated several excellent advantages in PFAOP preparation compared to enzymatic hydrolysis or chemical synthesis methods and provide a theoretical foundation for higher-value application of marine-derived functional peptides.

Synthesis and evaluation of arylpiperazine-reverse amides as biased dopamine D3 receptor ligands

( Yongkai Cao ),( Suresh Paudel ),( Xiaowei Zhang ),( Kyeong-man Kim ),( Seung Hoon Cheon ) 전남대학교 약품개발연구소 2015 약품개발연구지 Vol.24 No.-

The dopamine D3 receptor (D3R) preferential ligands have been universally adopted as a strategy for the treatment of drug addiction and other neuropsychiatric disorders due to fewer side effects. However, the high sequence homology between D3R and the D2 receptor (D2R) challenges the development of D3R-biased compounds. Herein. we design and synthesize a novel series of reverse amide-piperazine hybrid ligands and evaluate their biological affinities in vitro. Compound 4d was found to be the most potent D3R-selective ligand among these hybrid derivatives. Molecular modeling revealed that extracellular loop 1 (EL1) and loop 2 (EL2) of D3R together likely contribute to D3R selectivity over D2R. In particular. Gly94 in EL1 of D3R may act as a molecular determinant for D3R specificity.

Design, synthesis, and evaluation of bitopic arylpiperazine-phthalimides as selective dopamine D₃ receptor agonists

Cao, Yongkai,Sun, Ningning,Zhang, Jiumei,Liu, Zhiguo,Tang, Yi-zhe,Wu, Zhengzhi,Kim, Kyeong-Man,Cheon, Seung Hoon The Royal Society of Chemistry 2018 MedChemComm Vol.9 No.9

<P>The dopamine D3 receptor (D3R) is a proven therapeutic target for the treatment of neurological and neuropsychiatric disorders. In particular, D3R-selective ligands that can eliminate side effects associated with dopamine D2 receptor (D2R) therapeutics have been validated. However, the high homology in signaling pathways and the sequence similarity between D2R and D3R have rendered the development of D3R-selective ligands challenging. Herein, we designed and synthesized a series of piperazine-phthalimide bitopic ligands based on a fragment-based and molecular docking inspired design. Compound 9i was identified as the most selective D3R ligand among these bitopic ligands. Its selectivity was improved compared to reference compounds 1 and 2 by 9- and 2-fold, respectively, and it was 21-fold more potent than compound 2. Molecular docking demonstrated that the orientation of Leu<SUP>2.64</SUP> and Phe<SUP>7.39</SUP> and the packing at the junction of helices may affect the specificity for D3R over D2R. Functional evaluation revealed that D3R-selective ligand 9i displayed a subpicomolar agonist activity at D3R with a 199-fold increase in potency compared to quinpirole. These results may be useful for the fragment-based design of bitopic compounds as selective D3R ligands.</P>

A Novel Partial PPARα/γ Dual Agonist SN159 Improves Insulin Sensitivity

정유정,Yongkai Cao,Suresh Paudel,김기현,윤구,천승훈,Jee-Young Lee,김수남,김용기 대한화학회 2016 Bulletin of the Korean Chemical Society Vol.37 No.2

We here demonstrate that (E)-1-(3-aminophenyl)-3-(5-bromo-4-hydroxy-2-methoxyphenyl)prop-2-en-1-one (SN159) is a novel peroxisome proliferator-activated receptor (PPAR) partial agonist that improves insulin sensitivity. SN159 interacted directly with PPARα and PPARγ, which were confirmed by LanthaScreen ligand binding assay and molecular docking study. SN159 treatment leads to a significant improvement of insulin sensitivity, resulting in enhancing glucose uptake in muscle cells. SN159 stimulated adipogenic differentiation of 3T3-L1 preadipocytes, however, the effects were much weaker than those of PPARγ agonist troglitazone. In parallel, SN159 increased weakly the transcriptional activities of PPARα/γ, compared to the positive control. Furthermore, PPARγ activation and adipogenic differentiation by troglitazone were significantly reduced by treatment with SN159, indicating that SN159 is a partial agonist of PPARs. SN159 was able to enhance fatty acid oxidation and glucose utilization through the dual activation of PPARα/γ. Taken together, these results suggest that SN159 is a novel PPAR partial agonist, which can be used as potential therapeutic agents against type 2 diabetes and related metabolic disorders by enhancing glucose and lipid metabolism.

Concise synthesis of licochalcone C and its regioisomer, licochalcone H

Zengtao Wang,Yongkai Cao,Suresh Paudel,윤구,천승훈 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.12

Licochalone C (7a) is a retrochalcone isolatedfrom Glycyrrhiza inflata, which shows potent antioxidantproperties and inhibition of bacterial growth and cellularrespiration. Biological studies have suggested that licochalconeC attenuates the lipopolysaccharide and interferongammainduced inflammatory response by decreasing theexpression and activity of inducible nitric oxide synthaseand modulating the antioxidant network activity of superoxidedismutase, catalase, and glutathione peroxidaseactivity. Licochalcone C also inhibits NADH-cytochrome Creductase in the membrane fraction of Micrococcus luteus. Since pharmacological activity studies of licochalcone C areongoing and the yield of the compound is poor from naturalproduct, we report a concise four step synthesis of licochalconeC (7a) and its regioisomer, tentatively called licochalconeH (7b), by employing acid-mediated Claisen-Schmidt condensation as a key step with 6 and 20 % overallyield, respectively.

Preparation and Antioxidant Activities In Vitro of a Designed Antioxidant Peptide from Pinctada fucata by Recombinant Escherichia coli

( Yanyan Wu ),( Yongkai Ma ),( Laihao Li ),( Xianqing Yang ) 한국미생물생명공학회(구 한국산업미생물학회) 2018 Journal of microbiology and biotechnology Vol.28 No.1

An antioxidant peptide derived from Pinctada fucata meat using an Alcalase2.4L enzymatic hydrolysis method (named AOP) and identified by LC-TOF-MS has promising clinical potential for generating cosmetic products that protect skin from sunshine. To date, there have been few published studies investigating the structure-activity relationship in these peptides. To prepare antioxidant peptides better and improve their stability, the design and expression of an antioxidant peptide from Pinctada fucata (named DSAOP) was studied. The peptide contains a common precursor of an expression vector containing an α-helix tandemly linked according to the BamHI restriction sites. The DNA fragments encoding DSAOP were synthesized and subcloned into the expression vector pET-30a (+), and the peptide was expressed mostly as soluble protein in recombinant Escherichia coli. Meanwhile, the DPPH radical scavenging activity, superoxide radical scavenging activity, and hydroxyl radical scavenging activity of DSAOP IC50 values were 0.136 ± 0.006, 0.625 ± 0.025, and 0.306 ± 0.015 mg/ml, respectively, with 2-fold higher DPPH radical scavenging activity compared with chemosynthesized AOP (p < 0.05), as well as higher superoxide radical scavenging activity compared with natural AOP (p < 0.05). This preparation method was at the international advanced level. Furthermore, pilot-scale production results showed that DSAOP was expressed successfully in fermenter cultures, which indicated that the design strategy and expression methods would be useful for obtaining substantial amounts of stable peptides at low costs. These results showed that DSAOP produced with recombinant Escherichia coli could be useful in cosmetic skin care products, health foods, and pharmaceuticals.

A Ferrofluid-based Planar Damper with Magnetic Spring

Siqi Wang,Yongkai Liu,Decai Li 한국자기학회 2018 Journal of Magnetics Vol.23 No.3

The ferrofluid-based damper has been a subject of active research recently in depressing low-frequency vibration of rod due to its relative small viscous damping for the vibration pick-up system. In this work, a novel ferrofluid-based planar damper with magnetic spring is firstly proposed. Compared with the traditional ferrofluid-based damper with the elastic restoring force of ferrofluids, the novel damper is designed with steady magnetic spring to obtain a large relative displacement and dissipate external vibration energy efficiently. Experimental results show that the novel damper has a high damping performance. Under the same initial vibration amplitude of beam, the logarithmic decrement of the system with the novel damper is 31.5 times and 5.5 times larger than those of the system without damper and with the traditional damper, respectively. In addition, compared with the system with the traditional damper, the system with the novel damper can reduce damping time by half.

Design and synthesis of 4-benzylpiperidine carboxamides as dual serotonin and norepinephrine reuptake inhibitors

( Suresh Paudel ),( Yongkai Cao ),( Shuohan Guo ),( Byeongkwan An ),( Kyeong-man Kim ),( Seung Hoon Cheon ) 전남대학교 약품개발연구소 2015 약품개발연구지 Vol.24 No.-

A series of 4-benzylpiperidine carboxamides were designed and synthesized. and tested for their dual(serotonin and norepinephrine) reuptake inhibition. The synthesis of 4-benzylpiperidine carboxamides involved two main steps: amidation and substitution. Derivatives with 3 carbon linker displayed better activity than with 2 carbon linker. 4-Biphenyl- and 2-naphthyl-substituted derivatives 7e and 7j showed greater dual reuptake inhibition than standard drug venlafaxine HCI.

Research on an Outer Bound of Achievable Secrecy Rate Region for BCE

Yan Zhu,Xiao Chen,Yongkai Zhou,Fangbiao Li,Zhi Xue 보안공학연구지원센터 2014 International Journal of Hybrid Information Techno Vol.7 No.3

Investigation of the optimal fabrication of a single-carrier encapsulated fucoxanthin based on colloidal nanoparticles

Xin Zhang,Minghao Fan,Yongkai Yuan,Jianjun Dong,Hua Yin,Yang He,Lei Mao,Dongfeng Wang,Junhong Yu 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.114 No.-

Fucoxanthin (FX) is a carotenoid with antioxidant, anti-obesity, anti-diabetic, anti-cancer and antibacterialactivities. It is poorly water soluble and highly sensitive to light, heat and the surrounding environment. Therefore, how to effectively encapsulate it and stabilize it for entry into the human body hasbecome a key research question at present. This study developed a single-carrier to encapsulate FX andshowed excellent characterization results. The experimental results showed that the diameters of FX-ZHparticles prepared by the four encapsulation processes ranged from 143.83 to 216.93 nm. Comparison ofantioxidant activity and stability to temperature and pH of the four complexes showed significant differences,with the best performance of the nanoparticles prepared using water-soluble method and a slowspeedstirrer. The nanocomplexes were proved to be more stable and more bioavailable, with a significant34.41% increase in FX content relative to free FX in the intestinal phase. Inhibition of human leukaemiacells HL-60 cells remained high, with 11.14% ± 6.03% inhibition at FX concentrations of 1 lg/mL. Thisstudy encapsulated FX based on colloidal nanoparticle systems for the first time using a single-carriermaterial, an innovation and breakthrough that could simplify the experimental steps and provide thenecessary basis for industrial realization.