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Article ; Online: 2-Bromo-3-((1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazol-4-yl)-methoxy)-benzaldehyde

Xiaoyun Yun / Yuhan Xie / Jerome P. L. Ng / Betty Yuen Kwan Law / Vincent Kam Wai Wong / Paolo Coghi

Molbank, Vol 2022, Iss M1351, p M

2022 Volume 1351

Abstract: The 1,2,3-triazole ring system can be easily obtained by copper-catalyzed click reaction of azides with alkynes. 1,2,3-Triazole exhibits a myriad of biological activities, including antimalarial, antibacterial, and antiviral activities. We herein ... ...

Abstract	The 1,2,3-triazole ring system can be easily obtained by copper-catalyzed click reaction of azides with alkynes. 1,2,3-Triazole exhibits a myriad of biological activities, including antimalarial, antibacterial, and antiviral activities. We herein reported the synthesis of quinoline-based [ 1 , 2 , 3 ]-triazole hybrid via Cu(I)-catalyzed click reaction of 4-azido-7-chloroquinoline with alkyne derivative of 2-bromobenzaldehyde. The compound was fully characterized by proton nuclear magnetic resonance ( 1 H-NMR), carbon-13 nuclear magnetic resonance ( 13 C-NMR), heteronuclear single quantum coherence (HSQC), ultraviolet (UV), and high-resolution mass spectroscopies (HRMS). This compound was screened in vitro against two different normal cell lines. Preliminary studies attempted to evaluate its interaction with Delta RBD of spike protein of SARS-CoV-2 by bio-layer interferometry. Finally, the drug-likeness of the compound was also investigated by predicting its pharmacokinetic properties.
Keywords	1,2,3-triazole ; bio-layer interferometry ; RBD ; SARS-CoV-2 ; Inorganic chemistry ; QD146-197
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Two 18‐norspirostane steroidal saponins as novel mitophagy enhancers improve Alzheimer's disease

Wen‐Qiao Qiu / Lu Yu / Chang‐Long He / Jian‐Ming Wu / Betty Yuen‐Kwan Law / Chong‐Lin Yu / Da‐Lian Qin / Xiao‐Gang Zhou / An‐Guo Wu

Clinical and Translational Medicine, Vol 13, Iss 9, Pp n/a-n/a (2023)

2023

Keywords	Medicine (General) ; R5-920
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The potential development of drug resistance in rheumatoid arthritis patients identified with p53 mutations

Congling Qiu / Joyce Tsz Wai Chan / David Wei Zhang / Io Nam Wong / Yaling Zeng / Betty Yuen Kwan Law / Simon Wing Fai Mok / Ivo Ricardo De Seabra Rodrigues Dias / Wenfeng Liu / Liang Liu / Vincent Kam Wai Wong

Genes and Diseases, Vol 10, Iss 6, Pp 2252-

2023 Volume 2255

Keywords	Medicine (General) ; R5-920 ; Genetics ; QH426-470
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	KeAi Communications Co., Ltd.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Biological Evaluation in Resistant Cancer Cells and Study of Mechanism of Action of Arylvinyl-1,2,4-Trioxanes

Jerome P. L. Ng / Mohit K. Tiwari / Ali Adnan Nasim / Rui Long Zhang / Yuanqing Qu / Richa Sharma / Betty Yuen Kwan Law / Dharmendra K. Yadav / Sandeep Chaudhary / Paolo Coghi / Vincent Kam Wai Wong

Pharmaceuticals, Vol 15, Iss 360, p

2022 Volume 360

Abstract: 1,2,4-trioxane is a pharmacophore, which possesses a wide spectrum of biological activities, including anticancer effects. In this study, the cytotoxic effect and anticancer mechanism of action of a set of 10 selected peroxides were investigated on five ... ...

Abstract	1,2,4-trioxane is a pharmacophore, which possesses a wide spectrum of biological activities, including anticancer effects. In this study, the cytotoxic effect and anticancer mechanism of action of a set of 10 selected peroxides were investigated on five phenotypically different cancer cell lines (A549, A2780, HCT8, MCF7, and SGC7901) and their corresponding drug-resistant cancer cell lines. Among all peroxides, only 7 and 8 showed a better P-glycoprotein (P-gp) inhibitory effect at a concentration of 100 nM. These in vitro results were further validated by in silico docking and molecular dynamic (MD) studies, where compounds 7 and 8 exhibited docking scores of −7.089 and −8.196 kcal/mol, respectively, and remained generally stable in 100 ns during MD simulation. Further experiments revealed that peroxides 7 and 8 showed no significant effect on ROS accumulations and caspase-3 activity in A549 cells. Peroxides 7 and 8 were also found to decrease cell membrane potential. In addition, peroxides 7 and 8 were demonstrated to oxidize a flavin cofactor, possibly elucidating its mechanism of action. In conclusion, apoptosis induced by 1,2,4-trioxane was shown to undergo via a ROS- and caspase-3-independent pathway with hyperpolarization of cell membrane potential.
Keywords	1,2,4-trioxanes ; P-glycoprotein ; anticancer ; molecular docking ; mechanism of action ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Extracellular Vesicle Delivery of Neferine for the Attenuation of Neurodegenerative Disease Proteins and Motor Deficit in an Alzheimer’s Disease Mouse Model

Bin Tang / Wu Zeng / Lin Lin Song / Hui Miao Wang / Li Qun Qu / Hang Hong Lo / Lu Yu / An Guo Wu / Vincent Kam Wai Wong / Betty Yuen Kwan Law

Pharmaceuticals, Vol 15, Iss 83, p

2022 Volume 83

Abstract: Exosomes are nano-extracellular vesicles with diameters ranging from 30 to 150 nm, which are secreted by the cell. With their role in drug cargo loading, exosomes have been applied to carry compounds across the blood–brain barrier in order to target the ... ...

Abstract	Exosomes are nano-extracellular vesicles with diameters ranging from 30 to 150 nm, which are secreted by the cell. With their role in drug cargo loading, exosomes have been applied to carry compounds across the blood–brain barrier in order to target the central nervous system (CNS). In this study, high-purity exosomes isolated by the ultra-high-speed separation method were applied as the natural compound carrier, with the loading efficiency confirmed by UHPLC-MS analysis. Through the optimization of various cargo loading methods using exosomes, this study compared the efficiency of different ways for the separation of exosomes and the exosome encapsulation of natural compounds with increasing molecular weights via extensive in vitro and in vivo efficacy studies. In a pharmacokinetic study, our data suggested that the efficiency of compound’s loading into exosomes is positively correlated to its molecular weight. However, with a molecular weight of greater than 1109 Da, the exosome-encapsulated natural compounds were not able to pass through the blood–brain barrier (BBB). In vitro cellular models confirmed that three of the selected exosome-encapsulated natural compounds—baicalin, hederagenin and neferine—could reduce the level of neurodegenerative disease mutant proteins—including huntingtin 74 (HTT74), P301L tau and A53T α-synuclein (A53T α-syn)—more effectively than the compounds alone. With the traditional pharmacological role of the herbal plant Nelumbo nucifera in mitigating anxiety, exosome-encapsulated-neferine was, for the first time, reported to improve the motor deficits of APP/PS1 (amyloid precursor protein/ presenilin1) double transgenic mice, and to reduce the level of β-amyloid (Aβ) in the brain when compared with the same concentration of neferine alone. With the current trend in advocating medicine–food homology and green healthcare, this study has provided a rationale from in vitro to in vivo for the encapsulation of natural compounds using exosomes for the targeting of BBB permeability and ...
Keywords	exosomes ; neurodegenerative diseases ; compound carriers ; blood–brain barrier ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
Subject code	500
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Far infrared irradiation suppresses experimental arthritis in rats by down-regulation of genes involved inflammatory response and autoimmunity

Xi Chen / Hui Zhang / Wu Zeng / Nick Wang / Hang Hong Lo / Chi Kio Ip / Li Jun Yang / W.L. Wendy Hsiao / Wai Man Sin / Chenglai Xia / Betty Yuen Kwan Law / Vincent Kam Wai Wong

Journal of Advanced Research, Vol 38, Iss , Pp 107-

2022 Volume 118

Abstract: Introduction: Far-infrared radiation (FIR) is widely used in the treatment of various diseases such as insomnia and cardiovascular risk. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which the therapeutic potential of FIR in RA is ...

Abstract	Introduction: Far-infrared radiation (FIR) is widely used in the treatment of various diseases such as insomnia and cardiovascular risk. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which the therapeutic potential of FIR in RA is unclear. Objectives: To determine the therapeutic potential and mechanistic actions of FIR in treatment of RA. Methods: Adjuvant-induced arthritis (AIA) rat models were established to assess the therapeutic potency of FIR in RA treatment. The scoring parameters such as arthritis score, swelling of the hind paw, spleen and thymus indices, micro-CT analysis indices were adopted to estimate the beneficial effects of FIR during RA treatment in AIA model. PCR gene expression arrays were used to analyze inflammatory and autoimmune genes expression profiles in rat synovium. The inflammatory and immunity genes profiling was further analyzed through transcription factor prediction using PROMO. A signaling network map of possible molecular circuits connecting the identified differential genes to the RA's pathogenesis was constructed based on extensive literature reviews, and the major signaling pathways were validated by Western blotting. Results: Thirty minutes of FIR treatment significantly improved the symptoms of AIA in rats. Gene expression profiling indicated that 27 out of 370 genes were down-regulated by FIR. AP-1, CEBPα, CEBPβ, c-Fos, GR, HNF-3β, USF-1, and USF-2 were predicted as key transcription factors that regulated the identified differential genes. In addition, MAPK, PI3K-Akt, and NF-κB signaling are the major molecular pathways down-regulated by FIR treatment. Conclusion: FIR may provide beneficial effects on the AIA rat model of arthritis by suppression of the MAPK, PI3K-Akt and NF-κB signaling pathways. Therefore, we believe that FIR may provide an alternative non-pharmacological and non-surgical therapeutic approach for the treatment of RA.
Keywords	Far infrared irradiation (FIR) ; Adjuvant-induced arthritis (AIA) ; Inflammatory response ; Autoimmunity ; Transcription factors ; Medicine (General) ; R5-920 ; Science (General) ; Q1-390
Subject code	610
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hyperoside alleviates toxicity of β-amyloid via endoplasmic reticulum-mitochondrial calcium signal transduction cascade in APP/PS1 double transgenic Alzheimer's disease mice

Lin Lin Song / Yuan Qing Qu / Yong Pei Tang / Xi Chen / Hang Hong Lo / Li Qun Qu / Yun Xiao Yun / Vincent Kam Wai Wong / Rui Long Zhang / Hui Miao Wang / Meng Han Liu / Wei Zhang / Hui Xia Zhang / Joyce Tsz Wai Chan / Cai Ren Wang / Jian Hui Wu / Betty Yuen Kwan Law

Redox Biology, Vol 61, Iss , Pp 102637- (2023)

2023

Abstract: Alzheimer's disease is a neurodegenerative disorder characterized by a decline in cognitive function. The β-amyloid (Aβ) hypothesis suggests that Aβ peptides can spontaneously aggregate into β-fragment-containing oligomers and protofibrils, and this ... ...

Abstract	Alzheimer's disease is a neurodegenerative disorder characterized by a decline in cognitive function. The β-amyloid (Aβ) hypothesis suggests that Aβ peptides can spontaneously aggregate into β-fragment-containing oligomers and protofibrils, and this activation of the amyloid pathway alters Ca2+ signaling in neurons, leading to neurotoxicity and thus apoptosis of neuronal cells. In our study, a blood-brain barrier crossing flavonol glycoside hyperoside was identified with anti-Aβ aggregation, BACE inhibitory, and neuroprotective effect in cellular or APP/PSEN1 double transgenic Alzheimer's disease mice model. While our pharmacokinetic data confirmed that intranasal administration of hyperoside resulted in a higher bio-availability in mice brain, further in vivo studies revealed that it improved motor deficit, spatial memory and learning ability of APP/PSEN1 mice with reducing level of Aβ plaques and GFAP in the cortex and hippocampus. Bioinformatics, computational docking and in vitro assay results suggested that hyperoside bind to Aβ and interacted with ryanodine receptors, then regulated cellular apoptosis via endoplasmic reticulum-mitochondrial calcium (Ca2+) signaling pathway. Consistently, it was confirmed that hyperoside increased Bcl2, decreased Bax and cyto-c protein levels, and ameliorated neuronal cell death in both in vitro and in vivo model. By regulating Aβ-induced cell death via regulation on Ca2+ signaling cascade and mitochondrial membrane potential, our study suggested that hyperoside may work as a potential therapeutic agent or preventive remedy for Alzheimer's disease.
Keywords	Alzheimer's disease ; Aβ aggregates ; Hyperoside ; Neurotoxicity ; Endoplasmic reticulum-mitochondrial-Ca2+ ; Ryanodine receptors ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pharmacogenomics of Scopoletin in Tumor Cells

Ean-Jeong Seo / Mohamed Saeed / Betty Yuen Kwan Law / An Guo Wu / Onat Kadioglu / Henry Johannes Greten / Thomas Efferth

Molecules, Vol 21, Iss 4, p

2016 Volume 496

Abstract: Drug resistance and the severe side effects of chemotherapy necessitate the development of novel anticancer drugs. Natural products are a valuable source for drug development. Scopoletin is a coumarin compound, which can be found in several Artemisia ... ...

Abstract	Drug resistance and the severe side effects of chemotherapy necessitate the development of novel anticancer drugs. Natural products are a valuable source for drug development. Scopoletin is a coumarin compound, which can be found in several Artemisia species and other plant genera. Microarray-based RNA expression profiling of the NCI cell line panel showed that cellular response of scopoletin did not correlate to the expression of ATP-binding cassette (ABC) transporters as classical drug resistance mechanisms (ABCB1, ABCB5, ABCC1, ABCG2). This was also true for the expression of the oncogene EGFR and the mutational status of the tumor suppressor gene, TP53. However, mutations in the RAS oncogenes and the slow proliferative activity in terms of cell doubling times significantly correlated with scopoletin resistance. COMPARE and hierarchical cluster analyses of transcriptome-wide mRNA expression resulted in a set of 40 genes, which all harbored binding motifs in their promoter sequences for the transcription factor, NF-κB, which is known to be associated with drug resistance. RAS mutations, slow proliferative activity, and NF-κB may hamper its effectiveness. By in silico molecular docking studies, we found that scopoletin bound to NF-κB and its regulator IκB. Scopoletin activated NF-κB in a SEAP-driven NF-κB reporter cell line, indicating that NF-κB might be a resistance factor for scopoletin. In conclusion, scopoletin might serve as lead compound for drug development because of its favorable activity against tumor cells with ABC-transporter expression, although NF-κB activation may be considered as resistance factor for this compound. Further investigations are warranted to explore the full therapeutic potential of this natural product.
Keywords	ABC-transporter ; cluster analysis ; coumarin ; herbal medicine ; microarrays ; multidrug resistance ; phytotherapy ; Organic chemistry ; QD241-441
Subject code	500
Language	English
Publishing date	2016-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Neferine Attenuates the Protein Level and Toxicity of Mutant Huntingtin in PC-12 Cells via Induction of Autophagy

Vincent Kam Wai Wong / An Guo Wu / Jing Rong Wang / Liang Liu / Betty Yuen-Kwan Law

Molecules, Vol 20, Iss 3, Pp 3496-

2015 Volume 3514

Abstract: Mutant huntingtin aggregation is highly associated with the pathogenesis of Huntington’s disease, an adult-onset autosomal dominant disorder, which leads to a loss of motor control and decline in cognitive function. Recent literature has revealed the ... ...

Abstract	Mutant huntingtin aggregation is highly associated with the pathogenesis of Huntington’s disease, an adult-onset autosomal dominant disorder, which leads to a loss of motor control and decline in cognitive function. Recent literature has revealed the protective role of autophagy in neurodegenerative diseases through degradation of mutant toxic proteins, including huntingtin or a-synuclein. Through the GFP-LC3 autophagy detection platform, we have identified neferine, isolated from the lotus seed embryo of Nelumbo nucifera, which is able to induce autophagy through an AMPK-mTOR-dependent pathway. Furthermore, by overexpressing huntingtin with 74 CAG repeats (EGFP-HTT 74) in PC-12 cells, neferine reduces both the protein level and toxicity of mutant huntingtin through an autophagy-related gene 7 (Atg7)-dependent mechanism. With the variety of novel active compounds present in medicinal herbs, our current study suggests the possible protective mechanism of an autophagy inducer isolated from Chinese herbal medicine, which is crucial for its further development into a potential therapeutic agent for neurodegenerative disorders in the future.
Keywords	autophagy ; Nelumbo nucifera ; neferine ; AMPK ; mTOR ; a-synuclein ; huntingtin ; PC-12 ; bioactivity ; natural products ; mechanism of action ; Organic chemistry ; QD241-441
Language	English
Publishing date	2015-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: New Potential Pharmacological Functions of Chinese Herbal Medicines via Regulation of Autophagy

Betty Yuen Kwan Law / Simon Wing Fai Mok / An Guo Wu / Christopher Wai Kei Lam / Margaret Xin Yi Yu / Vincent Kam Wai Wong

Molecules, Vol 21, Iss 3, p

2016 Volume 359

Abstract: Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as ... ...

Abstract	Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as misfolded proteins or damaged organelles. Defects in autophagy are implicated in the pathogenesis of diseases including cancers, myopathy, neurodegenerations, infections and cardiovascular diseases. In the recent decade, traditional drugs with new clinical applications are not only commonly found in Western medicines, but also highlighted in Chinese herbal medicines (CHM). For instance, pharmacological studies have revealed that active components or fractions from Chaihu (Radix bupleuri), Hu Zhang (Rhizoma polygoni cuspidati), Donglingcao (Rabdosia rubesens), Hou po (Cortex magnoliae officinalis) and Chuan xiong (Rhizoma chuanxiong) modulate cancers, neurodegeneration and cardiovascular disease via autophagy. These findings shed light on the potential new applications and formulation of CHM decoctions via regulation of autophagy. This article reviews the roles of autophagy in the pharmacological actions of CHM and discusses their new potential clinical applications in various human diseases.
Keywords	autophagy ; natural products ; novel functions ; Chinese herbal medicines ; Organic chemistry ; QD241-441
Subject code	610
Language	English
Publishing date	2016-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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