Bifunctional backbone modified squaramide dipeptides as amyloid beta (A β) aggregation inhibitors
Bioorg Med Chem. 2023 Nov 30;97:117538. doi: 10.1016/j.bmc.2023.117538. Online ahead of print.ABSTRACTAlzheimer's disease (AD) is a devastating neurodegenerative condition with complex pathophysiology. Aggregated amyloid beta (Aβ) peptide plaques and higher concentrations of bio-metals such as copper (Cu), zinc (Zn), and iron (Fe) are the most significant hallmarks of AD observed in the brains of AD patients. Therefore simultaneous inhibition of Aβ peptide aggregation and reduction of metal stress may serve as an effective therapeutic approach for treating Alzheimer's disease. A series of bifunctional dipeptides bearing ...
Source: Bioorganic and Medicinal Chemistry - December 6, 2023 Category: Chemistry Authors: Suchita Dattatray Shinde Santosh Kumar Behera Neeraj Kulkarni Bhaskar Dewangan Bichismita Sahu Source Type: research
Bifunctional backbone modified squaramide dipeptides as amyloid beta (A β) aggregation inhibitors
Bioorg Med Chem. 2023 Nov 30;97:117538. doi: 10.1016/j.bmc.2023.117538. Online ahead of print.ABSTRACTAlzheimer's disease (AD) is a devastating neurodegenerative condition with complex pathophysiology. Aggregated amyloid beta (Aβ) peptide plaques and higher concentrations of bio-metals such as copper (Cu), zinc (Zn), and iron (Fe) are the most significant hallmarks of AD observed in the brains of AD patients. Therefore simultaneous inhibition of Aβ peptide aggregation and reduction of metal stress may serve as an effective therapeutic approach for treating Alzheimer's disease. A series of bifunctional dipeptides bearing ...
Source: Bioorganic and Medicinal Chemistry - December 6, 2023 Category: Chemistry Authors: Suchita Dattatray Shinde Santosh Kumar Behera Neeraj Kulkarni Bhaskar Dewangan Bichismita Sahu Source Type: research
Design, development and bio-evaluation of a novel radio-ligand < sup > 99m < /sup > Tc-THQ-DTPA as a sigma 2 receptor specific breast tumor imaging agent
Bioorg Med Chem. 2023 Nov 2;97:117515. doi: 10.1016/j.bmc.2023.117515. Online ahead of print.ABSTRACTOver-expression of sigma-2 receptor in cancer cells provides an opportunity to develop molecular probes for diagnosis, even for non-receptor specific malignancies like triple negative breast cancers. In this work, a novel sigma-2 receptor ligand [THQ-DTPA] has been synthesized and characterized using 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (THQ) and diethylenetriaminepentaacetic acid (DTPA). The ligand is further chelated with 99mTc for application as metal based radiotracer [99mTc-THQ-DTPA]. Radiolabelling with 99mTc ...
Source: Bioorganic and Medicinal Chemistry - December 3, 2023 Category: Chemistry Authors: Vishakha Chaudhary Shubhra Chaturvedi Anju Wadhwa Ritika Chaudhary Divya Gautam Deepika Sharma Rupesh Kumar A K Mishra Source Type: research
Design, development and bio-evaluation of a novel radio-ligand < sup > 99m < /sup > Tc-THQ-DTPA as a sigma 2 receptor specific breast tumor imaging agent
Bioorg Med Chem. 2023 Nov 2;97:117515. doi: 10.1016/j.bmc.2023.117515. Online ahead of print.ABSTRACTOver-expression of sigma-2 receptor in cancer cells provides an opportunity to develop molecular probes for diagnosis, even for non-receptor specific malignancies like triple negative breast cancers. In this work, a novel sigma-2 receptor ligand [THQ-DTPA] has been synthesized and characterized using 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (THQ) and diethylenetriaminepentaacetic acid (DTPA). The ligand is further chelated with 99mTc for application as metal based radiotracer [99mTc-THQ-DTPA]. Radiolabelling with 99mTc ...
Source: Bioorganic and Medicinal Chemistry - December 3, 2023 Category: Chemistry Authors: Vishakha Chaudhary Shubhra Chaturvedi Anju Wadhwa Ritika Chaudhary Divya Gautam Deepika Sharma Rupesh Kumar A K Mishra Source Type: research
Design, development and bio-evaluation of a novel radio-ligand < sup > 99m < /sup > Tc-THQ-DTPA as a sigma 2 receptor specific breast tumor imaging agent
Bioorg Med Chem. 2023 Nov 2;97:117515. doi: 10.1016/j.bmc.2023.117515. Online ahead of print.ABSTRACTOver-expression of sigma-2 receptor in cancer cells provides an opportunity to develop molecular probes for diagnosis, even for non-receptor specific malignancies like triple negative breast cancers. In this work, a novel sigma-2 receptor ligand [THQ-DTPA] has been synthesized and characterized using 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (THQ) and diethylenetriaminepentaacetic acid (DTPA). The ligand is further chelated with 99mTc for application as metal based radiotracer [99mTc-THQ-DTPA]. Radiolabelling with 99mTc ...
Source: Bioorganic and Medicinal Chemistry - December 3, 2023 Category: Chemistry Authors: Vishakha Chaudhary Shubhra Chaturvedi Anju Wadhwa Ritika Chaudhary Divya Gautam Deepika Sharma Rupesh Kumar A K Mishra 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
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
