Photodynamic anticancer activity evaluation of novel 5-aminolevulinic acid and 3-hydroxypyridinone conjugates
In conclusion, cellular phototoxicity showed a strong correlation with intracellular PpIX fluorescence levels, indicating the potential application of ALA-HPO conjugates in ALA-PDT.PMID:38626642 | DOI:10.1016/j.bmc.2024.117726 (Source: Bioorganic and Medicinal Chemistry)
Source: Bioorganic and Medicinal Chemistry - April 16, 2024 Category: Chemistry Authors: Jingqi Zhang Shengli Yuan Miaoliang Fan Keren Wang Jianan Guo Anjie Zang Jinhui Ren Weike Su Changjun Zhang Yuanyuan Xie Source Type: research
Photodynamic anticancer activity evaluation of novel 5-aminolevulinic acid and 3-hydroxypyridinone conjugates
In conclusion, cellular phototoxicity showed a strong correlation with intracellular PpIX fluorescence levels, indicating the potential application of ALA-HPO conjugates in ALA-PDT.PMID:38626642 | DOI:10.1016/j.bmc.2024.117726 (Source: Bioorganic and Medicinal Chemistry)
Source: Bioorganic and Medicinal Chemistry - April 16, 2024 Category: Chemistry Authors: Jingqi Zhang Shengli Yuan Miaoliang Fan Keren Wang Jianan Guo Anjie Zang Jinhui Ren Weike Su Changjun Zhang Yuanyuan Xie Source Type: research
Expanding the ligand spaces for E3 ligases for the design of protein degraders
Bioorg Med Chem. 2024 Apr 12;105:117718. doi: 10.1016/j.bmc.2024.117718. Online ahead of print.ABSTRACTTargeted protein degradation (TPD) has recently emerged as an exciting new drug modality. However, the strategy of developing small molecule-based protein degraders has evolved over the past two decades and has now established molecular tags that are already in clinical use, as well as chimeric molecules, PROteolysis TArgeting Chimeras (PROTACs), based mainly on ligand systems developed for the two E3 ligases CRBN and VHL. The large size of the human E3 ligase family suggests that PROTACs can be developed by targeting a l...
Source: Bioorganic and Medicinal Chemistry - April 15, 2024 Category: Chemistry Authors: Rahman Shah Zaib Saleem Martin P Schwalm Stefan Knapp Source Type: research
Expanding the ligand spaces for E3 ligases for the design of protein degraders
Bioorg Med Chem. 2024 Apr 12;105:117718. doi: 10.1016/j.bmc.2024.117718. Online ahead of print.ABSTRACTTargeted protein degradation (TPD) has recently emerged as an exciting new drug modality. However, the strategy of developing small molecule-based protein degraders has evolved over the past two decades and has now established molecular tags that are already in clinical use, as well as chimeric molecules, PROteolysis TArgeting Chimeras (PROTACs), based mainly on ligand systems developed for the two E3 ligases CRBN and VHL. The large size of the human E3 ligase family suggests that PROTACs can be developed by targeting a l...
Source: Bioorganic and Medicinal Chemistry - April 15, 2024 Category: Chemistry Authors: Rahman Shah Zaib Saleem Martin P Schwalm Stefan Knapp Source Type: research
A turn for the worse: A β β-hairpins in Alzheimer's disease
Bioorg Med Chem. 2024 Apr 10;105:117715. doi: 10.1016/j.bmc.2024.117715. Online ahead of print.ABSTRACTAmyloid-β (Aβ) oligomers are a cause of neurodegeneration in Alzheimer's disease (AD). These soluble aggregates of the Aβ peptide have proven difficult to study due to their inherent metastability and heterogeneity. Strategies to isolate and stabilize homogenous Aβ oligomer populations have emerged such as mutations, covalent cross-linking, and protein fusions. These strategies along with molecular dynamics simulations have provided a variety of proposed structures of Aβ oligomers, many of which consist of molecules ...
Source: Bioorganic and Medicinal Chemistry - April 14, 2024 Category: Chemistry Authors: Sarah M Ruttenberg James S Nowick Source Type: research
Synthesis and biological evaluation of EGFR binding peptides for near-infrared photoimmunotherapy
In this study, we developed a novel PIT drug using a peptide as the target-directed molecule. Epidermal growth factor receptor (EGFR) was selected as the target, and monovalent and bivalent EGFR-binding peptides were synthesized. The bivalent peptide showed sufficient binding to EGFR-positive cells, and a bivalent peptide-IR700 conjugate with a long linker induced morphological changes in EGFR-positive cells. Additionally, the drug significantly reduced cell viability in vitro in an NIR light-dose- and drug-concentration-dependent manner. These results indicate the feasibility of NIR-PIT in treating cancer using peptide-ba...
Source: Bioorganic and Medicinal Chemistry - April 13, 2024 Category: Chemistry Authors: Takuya Otani Motofumi Suzuki Hideo Takakura Hirofumi Hanaoka Source Type: research
Synthesis and biological evaluation of EGFR binding peptides for near-infrared photoimmunotherapy
In this study, we developed a novel PIT drug using a peptide as the target-directed molecule. Epidermal growth factor receptor (EGFR) was selected as the target, and monovalent and bivalent EGFR-binding peptides were synthesized. The bivalent peptide showed sufficient binding to EGFR-positive cells, and a bivalent peptide-IR700 conjugate with a long linker induced morphological changes in EGFR-positive cells. Additionally, the drug significantly reduced cell viability in vitro in an NIR light-dose- and drug-concentration-dependent manner. These results indicate the feasibility of NIR-PIT in treating cancer using peptide-ba...
Source: Bioorganic and Medicinal Chemistry - April 13, 2024 Category: Chemistry Authors: Takuya Otani Motofumi Suzuki Hideo Takakura Hirofumi Hanaoka Source Type: research
Design, synthesis, and evaluation of formylpiperazine analogs of Ferrostatin-1 as novel improved ferroptosis inhibitors
In this study, a series of new formylpiperazine-derived ferroptosis inhibitors were designed and synthesized based on the structure of a known ferroptosis inhibitor, ferrostatin-1 (Fer-1). The anti-ferroptosis activity of these synthetic compounds in human umbilical vein endothelial cells (HUVECs) induced by Erastin was evaluated. It was found that some of the new compounds, especially compound 26, showed potent anti-ferroptosis activity, as evidenced by its ability to restore cell viability, reduce iron accumulation, scavenge reactive oxygen species, maintain mitochondrial membrane potential, increase GSH levels, decrease...
Source: Bioorganic and Medicinal Chemistry - April 12, 2024 Category: Chemistry Authors: Hua-Long Ji Yi-Fan Zhang Nai-Yu Zhang Kai-Ming Wang Ning Meng Juan Zhang Cheng-Shi Jiang Source Type: research
SuFEx-based chemical diversification for the systematic discovery of CRBN molecular glues
Bioorg Med Chem. 2024 Apr 4;104:117699. doi: 10.1016/j.bmc.2024.117699. Online ahead of print.ABSTRACTMolecular glues are small molecules that stabilize protein-protein interactions, enabling new molecular pharmacologies, such as targeted protein degradation. They offer advantages over proteolysis targeting chimeras (PROTACs), which present challenges associated with the size and properties of heterobifunctional constructions, but glues lack the rational design principles analogous to PROTACs. One notable exception is the ability to alter the structure of Cereblon (CRBN)-based molecular glues and redirect their activity to...
Source: Bioorganic and Medicinal Chemistry - April 12, 2024 Category: Chemistry Authors: Trever R Carter Natalia Milosevich Lucas Dada James B Shaum K Barry Sharpless Seiya Kitamura Michael A Erb Source Type: research
Synthesis, radiosynthesis and biochemical evaluation of fluorinated analogues of sphingosine-1-phosphate receptor 3 specific antagonists using PET
Bioorg Med Chem. 2024 Mar 26;104:117697. doi: 10.1016/j.bmc.2024.117697. Online ahead of print.ABSTRACTSphingosine-1-phosphate and its receptors (S1PRs) are involved in several diseases such as auto immunity, inflammation and cardiovascular disorders. The S1P analogue fingolimod (Gilenya®) is currently in use for the treatment of relapsing multiple sclerosis. S1PRs are also promising targets for clinical molecular imaging in vivo. The organ distribution of individual S1PRs can be potentially achieved by using S1PR subtype-specific (radiolabeled) chemical probes. Here, we report our efforts on synthesis and in vivo potency...
Source: Bioorganic and Medicinal Chemistry - April 10, 2024 Category: Chemistry Authors: Vysakh Puspha Prasad Stefan Wagner Petra Keul Sven Hermann Bodo Levkau Michael Sch äfers G ünter Haufe Source Type: research
Synthesis, radiosynthesis and biochemical evaluation of fluorinated analogues of sphingosine-1-phosphate receptor 3 specific antagonists using PET
Bioorg Med Chem. 2024 Mar 26;104:117697. doi: 10.1016/j.bmc.2024.117697. Online ahead of print.ABSTRACTSphingosine-1-phosphate and its receptors (S1PRs) are involved in several diseases such as auto immunity, inflammation and cardiovascular disorders. The S1P analogue fingolimod (Gilenya®) is currently in use for the treatment of relapsing multiple sclerosis. S1PRs are also promising targets for clinical molecular imaging in vivo. The organ distribution of individual S1PRs can be potentially achieved by using S1PR subtype-specific (radiolabeled) chemical probes. Here, we report our efforts on synthesis and in vivo potency...
Source: Bioorganic and Medicinal Chemistry - April 10, 2024 Category: Chemistry Authors: Vysakh Puspha Prasad Stefan Wagner Petra Keul Sven Hermann Bodo Levkau Michael Sch äfers G ünter Haufe Source Type: research
Synthesis, radiosynthesis and biochemical evaluation of fluorinated analogues of sphingosine-1-phosphate receptor 3 specific antagonists using PET
Bioorg Med Chem. 2024 Mar 26;104:117697. doi: 10.1016/j.bmc.2024.117697. Online ahead of print.ABSTRACTSphingosine-1-phosphate and its receptors (S1PRs) are involved in several diseases such as auto immunity, inflammation and cardiovascular disorders. The S1P analogue fingolimod (Gilenya®) is currently in use for the treatment of relapsing multiple sclerosis. S1PRs are also promising targets for clinical molecular imaging in vivo. The organ distribution of individual S1PRs can be potentially achieved by using S1PR subtype-specific (radiolabeled) chemical probes. Here, we report our efforts on synthesis and in vivo potency...
Source: Bioorganic and Medicinal Chemistry - April 10, 2024 Category: Chemistry Authors: Vysakh Puspha Prasad Stefan Wagner Petra Keul Sven Hermann Bodo Levkau Michael Sch äfers G ünter Haufe Source Type: research
Human mitochondrial glutathione transferases: Kinetic parameters and accommodation of a mitochondria-targeting group in substrates
Bioorg Med Chem. 2024 Apr 3;104:117712. doi: 10.1016/j.bmc.2024.117712. Online ahead of print.ABSTRACTGlutathione-S-transferases are key to the cellular detoxification of xenobiotics and products of oxidative damage. GSTs catalyse the reaction of glutathione (GSH) with electrophiles to form stable thioether adducts. GSTK1-1 is the main GST isoform in the mitochondrial matrix, but the GSTA1-1 and GSTA4-4 isoforms are also thought to be in the mitochondria with their distribution altering in transformed cells, thus potentially providing a cancer specific target. A mitochondria-targeted version of the GST substrate 1-chloro-2...
Source: Bioorganic and Medicinal Chemistry - April 9, 2024 Category: Chemistry Authors: Patrick A Cardwell Carlo Del Moro Michael P Murphy Adrian J Lapthorn Richard C Hartley Source Type: research
Human mitochondrial glutathione transferases: Kinetic parameters and accommodation of a mitochondria-targeting group in substrates
Bioorg Med Chem. 2024 Apr 3;104:117712. doi: 10.1016/j.bmc.2024.117712. Online ahead of print.ABSTRACTGlutathione-S-transferases are key to the cellular detoxification of xenobiotics and products of oxidative damage. GSTs catalyse the reaction of glutathione (GSH) with electrophiles to form stable thioether adducts. GSTK1-1 is the main GST isoform in the mitochondrial matrix, but the GSTA1-1 and GSTA4-4 isoforms are also thought to be in the mitochondria with their distribution altering in transformed cells, thus potentially providing a cancer specific target. A mitochondria-targeted version of the GST substrate 1-chloro-2...
Source: Bioorganic and Medicinal Chemistry - April 9, 2024 Category: Chemistry Authors: Patrick A Cardwell Carlo Del Moro Michael P Murphy Adrian J Lapthorn Richard C Hartley Source Type: research
RNA sequences that direct selective ADAR editing from a SELEX library bearing 8-azanebularine
Bioorg Med Chem. 2024 Mar 29;104:117700. doi: 10.1016/j.bmc.2024.117700. Online ahead of print.ABSTRACTAdenosine Deaminases Acting on RNA (ADARs) catalyze the deamination of adenosine to inosine in double-stranded RNA (dsRNA). ADARs' ability to recognize and edit dsRNA is dependent on local sequence context surrounding the edited adenosine and the length of the duplex. A deeper understanding of how editing efficiency is affected by mismatches, loops, and bulges around the editing site would aid in the development of therapeutic gRNAs for ADAR-mediated site-directed RNA editing (SDRE). Here, a SELEX (systematic evolution of...
Source: Bioorganic and Medicinal Chemistry - April 7, 2024 Category: Chemistry Authors: Bailey L Wong Herra G Mendoza Casey S Jacobsen Peter A Beal Source Type: research
