Discovery of Potent Isoindolinone Inhibitors That Target an Active Conformation of PARP1 Using DNA-Encoded Libraries
ChemMedChem. 2024 Mar 14:e202400093. doi: 10.1002/cmdc.202400093. Online ahead of print.ABSTRACTInhibition of poly (ADP-ribose) polymerase-1 (PARP1), a DNA repair enzyme, has proven to be a successful strategy for the treatment of various cancers. With the appropriate selection conditions and protein design, DNA-encoded library (DEL) technology provides a powerful avenue to identify small molecules with the desired mechanism of action towards a target of interest. However, DNA-binding proteins, such as PARP1, can be challenging targets for DEL screening due to non-specific protein-DNA interactions. To overcome this, we des...
Source: ChemMedChem - March 14, 2024 Category: Chemistry Authors: Kelly A McCarthy Douglas J Marcotte Sangram Parelkar Crystal L McKinnon Lindsay E Trammell Eric L Stangeland Rachael R Jetson Source Type: research
Medical Applications of Silver and Gold Nanoparticles and Core-shell Nanostructures Based on Silver or Gold Core: Recent Progress and Innovations
ChemMedChem. 2024 Mar 13:e202300672. doi: 10.1002/cmdc.202300672. Online ahead of print.ABSTRACTNanoparticles (NPs) of noble metals such as silver (Ag NPs) or gold (Au NPs) draw the attention of scientists looking for new compounds to use in medical applications. Scientists have used metal NPs because of their easy preparation, biocompatibility, ability to influence the shape and size or modification, and surface functionalization. However, to fully use their capabilities, both the benefits and their potential threats should be considered. One possibility to reduce the potential threat and thus prevent the extinction of th...
Source: ChemMedChem - March 13, 2024 Category: Chemistry Authors: Kowalska Agata Adamska Elzbieta Beata Grobelna Source Type: research
Medical Applications of Silver and Gold Nanoparticles and Core-shell Nanostructures Based on Silver or Gold Core: Recent Progress and Innovations
ChemMedChem. 2024 Mar 13:e202300672. doi: 10.1002/cmdc.202300672. Online ahead of print.ABSTRACTNanoparticles (NPs) of noble metals such as silver (Ag NPs) or gold (Au NPs) draw the attention of scientists looking for new compounds to use in medical applications. Scientists have used metal NPs because of their easy preparation, biocompatibility, ability to influence the shape and size or modification, and surface functionalization. However, to fully use their capabilities, both the benefits and their potential threats should be considered. One possibility to reduce the potential threat and thus prevent the extinction of th...
Source: ChemMedChem - March 13, 2024 Category: Chemistry Authors: Kowalska Agata Adamska Elzbieta Beata Grobelna Source Type: research
Targeted Redox Balancing through Pulmonary Nanomedicine Delivery Reverses Oxidative Stress Induced Lung Inflammation
ChemMedChem. 2024 Mar 8:e202400037. doi: 10.1002/cmdc.202400037. Online ahead of print.ABSTRACTNon-invasive delivery of drugs is important for the reversal of respiratory diseases essentially by-passing metabolic pathways and targeting large surface area of drug absorption. Here, we study the inhalation of a redox nano medicine namely citrate functionalized Mn3O4 (C-Mn3O4) duly encapsulated in droplet evaporated aerosols for the balancing of oxidative stress generated by the exposure of Chromium (VI) ion, a potential lung carcinogenic agent. Our optical spectroscopic in-vitro experiments demonstrates the efficacy of redox ...
Source: ChemMedChem - March 9, 2024 Category: Chemistry Authors: Ria Ghosh Monojit Das Susmita Mondal Amrita Banerjee Lopamudra Roy Anjan Kumar Das Debasish Pal Siddhartha Sankar Bhattacharya Maitree Bhattacharyya Samir Kumar Pal Source Type: research
Targeted Redox Balancing through Pulmonary Nanomedicine Delivery Reverses Oxidative Stress Induced Lung Inflammation
ChemMedChem. 2024 Mar 8:e202400037. doi: 10.1002/cmdc.202400037. Online ahead of print.ABSTRACTNon-invasive delivery of drugs is important for the reversal of respiratory diseases essentially by-passing metabolic pathways and targeting large surface area of drug absorption. Here, we study the inhalation of a redox nano medicine namely citrate functionalized Mn3O4 (C-Mn3O4) duly encapsulated in droplet evaporated aerosols for the balancing of oxidative stress generated by the exposure of Chromium (VI) ion, a potential lung carcinogenic agent. Our optical spectroscopic in-vitro experiments demonstrates the efficacy of redox ...
Source: ChemMedChem - March 9, 2024 Category: Chemistry Authors: Ria Ghosh Monojit Das Susmita Mondal Amrita Banerjee Lopamudra Roy Anjan Kumar Das Debasish Pal Siddhartha Sankar Bhattacharya Maitree Bhattacharyya Samir Kumar Pal Source Type: research
Targeted Redox Balancing through Pulmonary Nanomedicine Delivery Reverses Oxidative Stress Induced Lung Inflammation
ChemMedChem. 2024 Mar 8:e202400037. doi: 10.1002/cmdc.202400037. Online ahead of print.ABSTRACTNon-invasive delivery of drugs is important for the reversal of respiratory diseases essentially by-passing metabolic pathways and targeting large surface area of drug absorption. Here, we study the inhalation of a redox nano medicine namely citrate functionalized Mn3O4 (C-Mn3O4) duly encapsulated in droplet evaporated aerosols for the balancing of oxidative stress generated by the exposure of Chromium (VI) ion, a potential lung carcinogenic agent. Our optical spectroscopic in-vitro experiments demonstrates the efficacy of redox ...
Source: ChemMedChem - March 9, 2024 Category: Chemistry Authors: Ria Ghosh Monojit Das Susmita Mondal Amrita Banerjee Lopamudra Roy Anjan Kumar Das Debasish Pal Siddhartha Sankar Bhattacharya Maitree Bhattacharyya Samir Kumar Pal Source Type: research
Targeted Redox Balancing through Pulmonary Nanomedicine Delivery Reverses Oxidative Stress Induced Lung Inflammation
ChemMedChem. 2024 Mar 8:e202400037. doi: 10.1002/cmdc.202400037. Online ahead of print.ABSTRACTNon-invasive delivery of drugs is important for the reversal of respiratory diseases essentially by-passing metabolic pathways and targeting large surface area of drug absorption. Here, we study the inhalation of a redox nano medicine namely citrate functionalized Mn3O4 (C-Mn3O4) duly encapsulated in droplet evaporated aerosols for the balancing of oxidative stress generated by the exposure of Chromium (VI) ion, a potential lung carcinogenic agent. Our optical spectroscopic in-vitro experiments demonstrates the efficacy of redox ...
Source: ChemMedChem - March 9, 2024 Category: Chemistry Authors: Ria Ghosh Monojit Das Susmita Mondal Amrita Banerjee Lopamudra Roy Anjan Kumar Das Debasish Pal Siddhartha Sankar Bhattacharya Maitree Bhattacharyya Samir Kumar Pal Source Type: research
Identification of Potential inhibitors of the SARS-CoV-2 NSP13 Helicase via Structure-Based Ligand Design, Molecular Docking and Nonequilibrium Alchemical Simulations
ChemMedChem. 2024 Mar 8:e202400095. doi: 10.1002/cmdc.202400095. Online ahead of print.ABSTRACTWe have assembled a computational pipeline based on virtual screening, docking techniques, and nonequilibrium molecular dynamics simulations, with the goal of identifying possible inhibitors of the SARS-CoV-2 NSP13 helicase, catalyzing by ATP hydrolysis the unwinding of double or single-stranded RNA in the viral replication process inside the host cell. The druggable sites for broad-spectrum inhibitors are represented by the RNA binding sites at the 5' entrance and 3' exit of the central channel, a structural motif that is highly...
Source: ChemMedChem - March 8, 2024 Category: Chemistry Authors: Giorgio Di Paco Marina Macchiagodena Piero Procacci Source Type: research
Identification of Potential inhibitors of the SARS-CoV-2 NSP13 Helicase via Structure-Based Ligand Design, Molecular Docking and Nonequilibrium Alchemical Simulations
ChemMedChem. 2024 Mar 8:e202400095. doi: 10.1002/cmdc.202400095. Online ahead of print.ABSTRACTWe have assembled a computational pipeline based on virtual screening, docking techniques, and nonequilibrium molecular dynamics simulations, with the goal of identifying possible inhibitors of the SARS-CoV-2 NSP13 helicase, catalyzing by ATP hydrolysis the unwinding of double or single-stranded RNA in the viral replication process inside the host cell. The druggable sites for broad-spectrum inhibitors are represented by the RNA binding sites at the 5' entrance and 3' exit of the central channel, a structural motif that is highly...
Source: ChemMedChem - March 8, 2024 Category: Chemistry Authors: Giorgio Di Paco Marina Macchiagodena Piero Procacci Source Type: research
Combinatorial libraries of bipodal binders of the insulin receptor
ChemMedChem. 2024 Mar 6:e202400145. doi: 10.1002/cmdc.202400145. Online ahead of print.ABSTRACTThe binding process of insulin to its transmembrane receptor entails a sophisticated interplay between two proteins, each possessing two binding sites. Given the difficulties associated with the use of insulin in the treatment of diabetes, despite its remarkable efficacy, there is interest in smaller and more stable compounds than the native hormone that would effectively activate the receptor. Our study adopts a strategy focused on synthesizing extensive combinatorial libraries of bipodal compounds consisting of two distinct pep...
Source: ChemMedChem - March 6, 2024 Category: Chemistry Authors: Irena Selicharova Benjamin Fabre Mar ía Soledad Garre Hernández Marta Lubos Jan Picha Zdenek Voburka Katar ína Mitrová Jiri Jiracek Source Type: research
Spiro-acridine Compound as a Pteridine Reductase 1 Inhibitor: in silico Target Fishing and in vitro Studies
ChemMedChem. 2024 Mar 6:e202300545. doi: 10.1002/cmdc.202300545. Online ahead of print.ABSTRACTAmong the many neglected tropical diseases, Leishmaniasis ranks second in mortality rate and prevalence. In a previous study, acridine derivatives were synthesized and tested for their antileishmanial activity against L. chagasi. The most active compound identified in that study (1) showed a single digit EC50 value against the parasite (2.6 µM), but its macromolecular target remained unknown. Aiming to overcome this limitation, this work exploited inverse virtual screening to identify compound 1's putative molecular mechanism of...
Source: ChemMedChem - March 6, 2024 Category: Chemistry Authors: J éssika de Oliveira Viana Marina Sena Mendes Marcelo Santos Castilho Ricardo Ol ímpio de Moura Euz ébio Guimarães Barbosa Source Type: research
Combinatorial libraries of bipodal binders of the insulin receptor
ChemMedChem. 2024 Mar 6:e202400145. doi: 10.1002/cmdc.202400145. Online ahead of print.ABSTRACTThe binding process of insulin to its transmembrane receptor entails a sophisticated interplay between two proteins, each possessing two binding sites. Given the difficulties associated with the use of insulin in the treatment of diabetes, despite its remarkable efficacy, there is interest in smaller and more stable compounds than the native hormone that would effectively activate the receptor. Our study adopts a strategy focused on synthesizing extensive combinatorial libraries of bipodal compounds consisting of two distinct pep...
Source: ChemMedChem - March 6, 2024 Category: Chemistry Authors: Irena Selicharova Benjamin Fabre Mar ía Soledad Garre Hernández Marta Lubos Jan Picha Zdenek Voburka Katar ína Mitrová Jiri Jiracek Source Type: research
Spiro-acridine Compound as a Pteridine Reductase 1 Inhibitor: in silico Target Fishing and in vitro Studies
ChemMedChem. 2024 Mar 6:e202300545. doi: 10.1002/cmdc.202300545. Online ahead of print.ABSTRACTAmong the many neglected tropical diseases, Leishmaniasis ranks second in mortality rate and prevalence. In a previous study, acridine derivatives were synthesized and tested for their antileishmanial activity against L. chagasi. The most active compound identified in that study (1) showed a single digit EC50 value against the parasite (2.6 µM), but its macromolecular target remained unknown. Aiming to overcome this limitation, this work exploited inverse virtual screening to identify compound 1's putative molecular mechanism of...
Source: ChemMedChem - March 6, 2024 Category: Chemistry Authors: J éssika de Oliveira Viana Marina Sena Mendes Marcelo Santos Castilho Ricardo Ol ímpio de Moura Euz ébio Guimarães Barbosa Source Type: research
Copper and Copper Complexes in Tumor Therapy
ChemMedChem. 2024 Mar 5:e202400060. doi: 10.1002/cmdc.202400060. Online ahead of print.ABSTRACTCopper (Cu), a crucial trace element in physiological processes, has garnered significant interest for its involvement in cancer progression and potential therapeutic applications. The regulation of cellular copper levels is essential for maintaining copper homeostasis, as imbalances can lead to toxicity and cell death. The development of drugs that target copper homeostasis has emerged as a promising strategy for anticancer treatment, with a particular focus on copper chelators, copper ionophores, and novel copper complexes. Rec...
Source: ChemMedChem - March 5, 2024 Category: Chemistry Authors: Yingqiao Wang Tingxi Tang Yi Yuan Nan Li Xiaoqing Wang Jian Guan Source Type: research
Design, synthesis, and biological evaluation of eukaryotic initiation factor 2B (eIF2B) activators
ChemMedChem. 2024 Mar 1:e202300716. doi: 10.1002/cmdc.202300716. Online ahead of print.ABSTRACTThe eukaryotic initiation factor 2B (eIF2B) is a key regulator in protein-regulated signaling pathways and is closely related to the function of the central nervous system. Modulating eIF2B could retard the process of neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and vanishing white matter disease (VWM) et al. Here, we designed and synthesized a series of novel eIF2B activators containing oxadiazole fragments. The activating effects of compounds on eIF2B were investigated thr...
Source: ChemMedChem - March 1, 2024 Category: Chemistry Authors: Yifeng Pei Sentao Liu Lixun Wang Chao Chen Mengqiu Hu Yi Xue Dezhong Guan Lingfeng Xie Hong Liao Jinpei Zhou Huibin Zhang Source Type: research
