1592907-45-3Relevant academic research and scientific papers
Prevention of mitochondrial membrane permeabilization and pancreatic β-cell death by an enantioenriched, macrocyclic small molecule
Jimmidi, Ravikumar,Shroff, Govardhan K.,Satyanarayana,Reddy, B. Ramesh,Kapireddy, Jahnavi,Sawant, Mithila A.,Sitaswad, Sandhya L.,Arya, Prabhat,Mitra, Prasenjit
supporting information, p. 1151 - 1156 (2014/03/21)
Mitochondria produce the majority of cellular energy through the process of oxidative phosphorylation and play a central role in regulating the functionality and survival of eukaryotic cells. Under physiological stress, mitochondrial membrane permeabilization results in the release of apoptogenic material such as cytochrome c in the cytoplasm, which thereby initiates caspase activation and the consequent cell death. In our present study, we screened a series of compounds for their ability to inhibit mitochondrial membrane permeabilization and to prevent cytochrome c release during the endoplasmic reticulum stress in cultured pancreatic β-cells. Three benzofuran-based macrocyclic small molecules, that is, 2.4c, c104, and c108, were found to restore the depolarization of mitochondrial membrane potential and to prevent the release of cytochrome c from mitochondria. Interestingly, the acyclic precursor of 2.4c (i.e., 2.3c) did not show any effect, whereas the macrocyclic derivative obtained by utilizing ring-closing metathesis as the "stitching technology" led to this function. The macrocyclic architecture seems to play a crucial role in presenting various functional moieties in the right orientation to observe this effect. A series of compounds for their ability to inhibit mitochondrial membrane permeabilization and to prevent cytochrome c release during endoplasmic reticulum stress in cultured pancreatic β-cells is screened. Three benzofuran-based macrocyclic small molecules were found to restore the depolarization of the mitochondrial membrane potential and to prevent the release of cytochrome c from mitochondria. MPTP = Mitochondrial Permeability Transition Pore. Copyright
Prevention of Mitochondrial Membrane Permeabilization and Pancreatic β-Cell Death by an Enantioenriched, Macrocyclic Small Molecule
Jimmidi, Ravikumar,Shroff, Govardhan K.,Satyanarayana,Reddy, B. Ramesh,Kapireddy, Jahnavi,Sawant, Mithila A.,Sitaswad, Sandhya L.,Arya, Prabhat,Mitra, Prasenjit
supporting information, p. 1151 - 1156 (2015/10/05)
Mitochondria produce the majority of cellular energy through the process of oxidative phosphorylation and play a central role in regulating the functionality and survival of eukaryotic cells. Under physiological stress, mitochondrial membrane permeabilization results in the release of apoptogenic material such as cytochrome c in the cytoplasm, which thereby initiates caspase activation and the consequent cell death. In our present study, we screened a series of compounds for their ability to inhibit mitochondrial membrane permeabilization and to prevent cytochrome c release during the endoplasmic reticulum stress in cultured pancreatic β-cells. Three benzofuran-based macrocyclic small molecules, that is, 2.4c, c104, and c108, were found to restore the depolarization of mitochondrial membrane potential and to prevent the release of cytochrome c from mitochondria. Interestingly, the acyclic precursor of 2.4c (i.e., 2.3c) did not show any effect, whereas the macrocyclic derivative obtained by utilizing ring-closing metathesis as the "stitching technology" led to this function. The macrocyclic architecture seems to play a crucial role in presenting various functional moieties in the right orientation to observe this effect.
