Hesperidin Methyl Chalcone reduces extracellular A β < sub > (25-35) < /sub > peptide aggregation and fibrillation and also protects Neuro 2a cells from A β < sub > (25-35) < /sub > induced neuronal dysfunction
Bioorg Med Chem. 2023 Nov 18;96:117536. doi: 10.1016/j.bmc.2023.117536. Online ahead of print.ABSTRACTIn the present study, we evaluated the neuroprotective potential of Hesperidin Methyl Chalcone (HMC) against the neurotoxicity induced by Aβ(25-35) peptide. HMC demonstrated higher free-radical scavenging activity than Hesperidin in initial cell-free studies. Investigations using the fluorescent dye thioflavin T with Aβ(25-35) peptide showed that HMC has the ability to combat extracellular amyloid aggregation by possessing anti-aggregation property against oligomers and by disaggregating mature fibrils. Also, the results...
Source: Bioorganic and Medicinal Chemistry - November 28, 2023 Category: Chemistry Authors: Sakthivel Jafni Sethuraman Sathya Malaisamy Arunkumar Chandramohan Kiruthiga Mahalingam Jeyakumar Easwaran Murugesh Kasi Pandima Devi Source Type: research
Hesperidin Methyl Chalcone reduces extracellular A β < sub > (25-35) < /sub > peptide aggregation and fibrillation and also protects Neuro 2a cells from A β < sub > (25-35) < /sub > induced neuronal dysfunction
Bioorg Med Chem. 2023 Nov 18;96:117536. doi: 10.1016/j.bmc.2023.117536. Online ahead of print.ABSTRACTIn the present study, we evaluated the neuroprotective potential of Hesperidin Methyl Chalcone (HMC) against the neurotoxicity induced by Aβ(25-35) peptide. HMC demonstrated higher free-radical scavenging activity than Hesperidin in initial cell-free studies. Investigations using the fluorescent dye thioflavin T with Aβ(25-35) peptide showed that HMC has the ability to combat extracellular amyloid aggregation by possessing anti-aggregation property against oligomers and by disaggregating mature fibrils. Also, the results...
Source: Bioorganic and Medicinal Chemistry - November 28, 2023 Category: Chemistry Authors: Sakthivel Jafni Sethuraman Sathya Malaisamy Arunkumar Chandramohan Kiruthiga Mahalingam Jeyakumar Easwaran Murugesh Kasi Pandima Devi Source Type: research
Hesperidin Methyl Chalcone reduces extracellular A β < sub > (25-35) < /sub > peptide aggregation and fibrillation and also protects Neuro 2a cells from A β < sub > (25-35) < /sub > induced neuronal dysfunction
Bioorg Med Chem. 2023 Nov 18;96:117536. doi: 10.1016/j.bmc.2023.117536. Online ahead of print.ABSTRACTIn the present study, we evaluated the neuroprotective potential of Hesperidin Methyl Chalcone (HMC) against the neurotoxicity induced by Aβ(25-35) peptide. HMC demonstrated higher free-radical scavenging activity than Hesperidin in initial cell-free studies. Investigations using the fluorescent dye thioflavin T with Aβ(25-35) peptide showed that HMC has the ability to combat extracellular amyloid aggregation by possessing anti-aggregation property against oligomers and by disaggregating mature fibrils. Also, the results...
Source: Bioorganic and Medicinal Chemistry - November 28, 2023 Category: Chemistry Authors: Sakthivel Jafni Sethuraman Sathya Malaisamy Arunkumar Chandramohan Kiruthiga Mahalingam Jeyakumar Easwaran Murugesh Kasi Pandima Devi Source Type: research
Hesperidin Methyl Chalcone reduces extracellular A β < sub > (25-35) < /sub > peptide aggregation and fibrillation and also protects Neuro 2a cells from A β < sub > (25-35) < /sub > induced neuronal dysfunction
Bioorg Med Chem. 2023 Nov 18;96:117536. doi: 10.1016/j.bmc.2023.117536. Online ahead of print.ABSTRACTIn the present study, we evaluated the neuroprotective potential of Hesperidin Methyl Chalcone (HMC) against the neurotoxicity induced by Aβ(25-35) peptide. HMC demonstrated higher free-radical scavenging activity than Hesperidin in initial cell-free studies. Investigations using the fluorescent dye thioflavin T with Aβ(25-35) peptide showed that HMC has the ability to combat extracellular amyloid aggregation by possessing anti-aggregation property against oligomers and by disaggregating mature fibrils. Also, the results...
Source: Bioorganic and Medicinal Chemistry - November 28, 2023 Category: Chemistry Authors: Sakthivel Jafni Sethuraman Sathya Malaisamy Arunkumar Chandramohan Kiruthiga Mahalingam Jeyakumar Easwaran Murugesh Kasi Pandima Devi Source Type: research
Glutathione-responsive PROTAC for targeted degradation of ER α in breast cancer cells
This study provides a potentially valuable strategy for breast cancer treatment using tumor microenvironment-responsive PROTACs.PMID:38008041 | DOI:10.1016/j.bmc.2023.117526 (Source: Bioorganic and Medicinal Chemistry)
Source: Bioorganic and Medicinal Chemistry - November 26, 2023 Category: Chemistry Authors: Zhili Zhou Heli Fan Dehao Yu Fengying Shi Qianqian Li Zhenjian Zhang Xiaolu Wang Xuejun Zhang Cheng Dong Huabing Sun Wenyi Mi Source Type: research
Glutathione-responsive PROTAC for targeted degradation of ER α in breast cancer cells
This study provides a potentially valuable strategy for breast cancer treatment using tumor microenvironment-responsive PROTACs.PMID:38008041 | DOI:10.1016/j.bmc.2023.117526 (Source: Bioorganic and Medicinal Chemistry)
Source: Bioorganic and Medicinal Chemistry - November 26, 2023 Category: Chemistry Authors: Zhili Zhou Heli Fan Dehao Yu Fengying Shi Qianqian Li Zhenjian Zhang Xiaolu Wang Xuejun Zhang Cheng Dong Huabing Sun Wenyi Mi Source Type: research
Discovery of conformationally constrained c-Abl inhibitors with potential neuroprotective effects against Parkinson's disease
Bioorg Med Chem. 2023 Nov 10;96:117532. doi: 10.1016/j.bmc.2023.117532. Online ahead of print.ABSTRACTAbelson tyrosine kinase (c-Abl) is involved in various biological processes in neurodegenerative diseases and is an attractive target for anti-PD (Parkinson's disease) drug discovery. Based on our previous work, we designed several novel c-Abl inhibitors through a conformational constrained strategy and evaluated their pharmacological activities. Among them, compound A6 exhibited superior inhibitory activity against c-Abl than nilotinib in the homogenous time-resolved fluorescence (HTRF) assay. Furthermore, A6 displayed hi...
Source: Bioorganic and Medicinal Chemistry - November 25, 2023 Category: Chemistry Authors: Zichao Yang Yangcheng Ai Guowu Wu Fengqiu Guo Zilong Yang Beijun Cheng Lishun Zhang Mingxia Li Jianjun Chen Jiajie Zhang Tingting Zhang Source Type: research
Discovery of conformationally constrained c-Abl inhibitors with potential neuroprotective effects against Parkinson's disease
Bioorg Med Chem. 2023 Nov 10;96:117532. doi: 10.1016/j.bmc.2023.117532. Online ahead of print.ABSTRACTAbelson tyrosine kinase (c-Abl) is involved in various biological processes in neurodegenerative diseases and is an attractive target for anti-PD (Parkinson's disease) drug discovery. Based on our previous work, we designed several novel c-Abl inhibitors through a conformational constrained strategy and evaluated their pharmacological activities. Among them, compound A6 exhibited superior inhibitory activity against c-Abl than nilotinib in the homogenous time-resolved fluorescence (HTRF) assay. Furthermore, A6 displayed hi...
Source: Bioorganic and Medicinal Chemistry - November 25, 2023 Category: Chemistry Authors: Zichao Yang Yangcheng Ai Guowu Wu Fengqiu Guo Zilong Yang Beijun Cheng Lishun Zhang Mingxia Li Jianjun Chen Jiajie Zhang Tingting Zhang Source Type: research
Beyond traditional methods: Unveiling the skin whitening properties of Rhein-Embedded PROTACs
In this study, we focused on tyrosinase (TYR), a key enzyme involved in melanin synthesis and pigmentation. For this target, we designed and synthesized a series of PROTACs (D3-D9), employing Rhein as the target protein-ligand. Through some experimental tests, we made a significant discovery. Preliminary experimental results show that the most promising compound (D6) demonstrated the ability to degrade MITF and inhibit the expression and TYR in B16-F10 cells, effectively suppressing melanogenesis in zebrafish. Notably, at equivalent concentrations, the whitening effect of D6 surpassed that of its precursor Rhein and was ev...
Source: Bioorganic and Medicinal Chemistry - November 22, 2023 Category: Chemistry Authors: Meng Xu Ziqing Zhang Peixi Zhang Qiaolai Wang Yuanxi Xia Chenlei Lian Jia Liu Jieqing Liu Source Type: research
Beyond traditional methods: Unveiling the skin whitening properties of Rhein-Embedded PROTACs
In this study, we focused on tyrosinase (TYR), a key enzyme involved in melanin synthesis and pigmentation. For this target, we designed and synthesized a series of PROTACs (D3-D9), employing Rhein as the target protein-ligand. Through some experimental tests, we made a significant discovery. Preliminary experimental results show that the most promising compound (D6) demonstrated the ability to degrade MITF and inhibit the expression and TYR in B16-F10 cells, effectively suppressing melanogenesis in zebrafish. Notably, at equivalent concentrations, the whitening effect of D6 surpassed that of its precursor Rhein and was ev...
Source: Bioorganic and Medicinal Chemistry - November 22, 2023 Category: Chemistry Authors: Meng Xu Ziqing Zhang Peixi Zhang Qiaolai Wang Yuanxi Xia Chenlei Lian Jia Liu Jieqing Liu Source Type: research
Beyond traditional methods: Unveiling the skin whitening properties of Rhein-Embedded PROTACs
In this study, we focused on tyrosinase (TYR), a key enzyme involved in melanin synthesis and pigmentation. For this target, we designed and synthesized a series of PROTACs (D3-D9), employing Rhein as the target protein-ligand. Through some experimental tests, we made a significant discovery. Preliminary experimental results show that the most promising compound (D6) demonstrated the ability to degrade MITF and inhibit the expression and TYR in B16-F10 cells, effectively suppressing melanogenesis in zebrafish. Notably, at equivalent concentrations, the whitening effect of D6 surpassed that of its precursor Rhein and was ev...
Source: Bioorganic and Medicinal Chemistry - November 22, 2023 Category: Chemistry Authors: Meng Xu Ziqing Zhang Peixi Zhang Qiaolai Wang Yuanxi Xia Chenlei Lian Jia Liu Jieqing Liu Source Type: research
Review and prospects of targeted therapies for Spleen tyrosine kinase (SYK)
This article reviews the biological function of SYK, the relationship between SYK and disease, and therapies targeting SYK. In addition, inspired by new technologies such as proteolysis targeting chimeras (PROTACs) and phosphatase recruiting chimeras (PHORCs), we propose the development of new therapeutic approaches for targeting SYK, such as SYK PROTACs and SYK PHORCs, which may overcome deficiencies of existing methods.PMID:37984216 | DOI:10.1016/j.bmc.2023.117514 (Source: Bioorganic and Medicinal Chemistry)
Source: Bioorganic and Medicinal Chemistry - November 20, 2023 Category: Chemistry Authors: Zhaozhao Wang Shu Qu Jiahao Yuan Wen Tian Jinglei Xu Rui Tao Shilong Sun Tao Lu Weifang Tang Yong Zhu Source Type: research
Review and prospects of targeted therapies for Spleen tyrosine kinase (SYK)
This article reviews the biological function of SYK, the relationship between SYK and disease, and therapies targeting SYK. In addition, inspired by new technologies such as proteolysis targeting chimeras (PROTACs) and phosphatase recruiting chimeras (PHORCs), we propose the development of new therapeutic approaches for targeting SYK, such as SYK PROTACs and SYK PHORCs, which may overcome deficiencies of existing methods.PMID:37984216 | DOI:10.1016/j.bmc.2023.117514 (Source: Bioorganic and Medicinal Chemistry)
Source: Bioorganic and Medicinal Chemistry - November 20, 2023 Category: Chemistry Authors: Zhaozhao Wang Shu Qu Jiahao Yuan Wen Tian Jinglei Xu Rui Tao Shilong Sun Tao Lu Weifang Tang Yong Zhu Source Type: research
In situ click chemistry-based discovery of 1,2,3-triazole-derived diarylpyrimidines as novel HIV-1 NNRTIs by exploiting the tolerant region I in binding pocket
Bioorg Med Chem. 2023 Sep 23;96:117484. doi: 10.1016/j.bmc.2023.117484. Online ahead of print.ABSTRACTHIV-1 reverse transcriptase (RT) is considered as one of the most significant targets for the anti-HIV-1 drug design due to their determined mechanism and well-decoded crystal structure. As a part of our continuous efforts towards the development of potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) by exploiting the tolerant region I of NNRTIs binding pocket (NNIBP), the miniaturized parallel synthesis via CuAAC click chemistry reaction followed by in situ biological screening have been performed in thi...
Source: Bioorganic and Medicinal Chemistry - November 17, 2023 Category: Chemistry Authors: Yanying Sun Da Feng Zhenzhen Zhou Tao Zhang Erik De Clercq Christophe Pannecouque Dongwei Kang Peng Zhan Xinyong Liu Source Type: research
Discovery of a novel GPR35 agonist with high and equipotent species potency for oral treatment of IBD
In this study, structural modifications to lodoxamide provides a series of high and equivalent agonists on human, mouse, and rat GPR35. These molecules eliminate the species selectivity of human to mouse and rat orthologs that have been prevalent with GPR35 agonists including lodoxamide. The cLogP properties are also optimized to make the compounds more obedient to drug-like rules, yielding compound 4b (cLogP = 2.41), which activates human, mouse or rat GPR35 with EC50 values of 76.0, 63.7 and 77.8 nM, respectively. Oral administration of compound 4b at 20 mg/kg alleviates clinical symptoms of DSS-induced IBD in mice, and ...
Source: Bioorganic and Medicinal Chemistry - November 17, 2023 Category: Chemistry Authors: Zhaoxiang Song Dan Lu Jun Sun Yangliang Ye Jiahui Fang Kai Wang Shimeng Guo Qing Zhang Xinheng He Xin Xie Jianhua Shen Source Type: research
