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

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

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

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

Chimeric Amphiphilic Disinfectants: Quaternary Ammonium / Quaternary Phosphonium Hybrid Structures
ChemMedChem. 2024 Feb 28:e202300718. doi: 10.1002/cmdc.202300718. Online ahead of print.ABSTRACTCationic biocides play a crucial role in the disinfection of domestic and healthcare surfaces. Due to the rise of bacterial resistance towards common cationic disinfectants like quaternary ammonium compounds (QACs), the development of novel actives is necessary for effective infection prevention and control. Toward this end, a series of 15 chimeric biscationic amphiphilic compounds, bearing both ammonium and phosphonium residues, were prepared to probe the structure and efficacy of mixed cationic ammonium-phosphonium structures....
Source: ChemMedChem - February 28, 2024 Category: Chemistry Authors: Moneya S Leatherbury Laura Thierer Christian A Sanchez Germ án Vargas-Cuebas Ashley A Petersen Lauren E Amoo Elise L Bezold Keshyne C Washington M Brody Mistrot Michael J Zdilla William M Wuest Kevin P C Minbiole Source Type: research

Chimeric Amphiphilic Disinfectants: Quaternary Ammonium / Quaternary Phosphonium Hybrid Structures
ChemMedChem. 2024 Feb 28:e202300718. doi: 10.1002/cmdc.202300718. Online ahead of print.ABSTRACTCationic biocides play a crucial role in the disinfection of domestic and healthcare surfaces. Due to the rise of bacterial resistance towards common cationic disinfectants like quaternary ammonium compounds (QACs), the development of novel actives is necessary for effective infection prevention and control. Toward this end, a series of 15 chimeric biscationic amphiphilic compounds, bearing both ammonium and phosphonium residues, were prepared to probe the structure and efficacy of mixed cationic ammonium-phosphonium structures....
Source: ChemMedChem - February 28, 2024 Category: Chemistry Authors: Moneya S Leatherbury Laura Thierer Christian A Sanchez Germ án Vargas-Cuebas Ashley A Petersen Lauren E Amoo Elise L Bezold Keshyne C Washington M Brody Mistrot Michael J Zdilla William M Wuest Kevin P C Minbiole Source Type: research

Chimeric Amphiphilic Disinfectants: Quaternary Ammonium / Quaternary Phosphonium Hybrid Structures
ChemMedChem. 2024 Feb 28:e202300718. doi: 10.1002/cmdc.202300718. Online ahead of print.ABSTRACTCationic biocides play a crucial role in the disinfection of domestic and healthcare surfaces. Due to the rise of bacterial resistance towards common cationic disinfectants like quaternary ammonium compounds (QACs), the development of novel actives is necessary for effective infection prevention and control. Toward this end, a series of 15 chimeric biscationic amphiphilic compounds, bearing both ammonium and phosphonium residues, were prepared to probe the structure and efficacy of mixed cationic ammonium-phosphonium structures....
Source: ChemMedChem - February 28, 2024 Category: Chemistry Authors: Moneya S Leatherbury Laura Thierer Christian A Sanchez Germ án Vargas-Cuebas Ashley A Petersen Lauren E Amoo Elise L Bezold Keshyne C Washington M Brody Mistrot Michael J Zdilla William M Wuest Kevin P C Minbiole Source Type: research

The amphipathic design in helical antimicrobial peptides
ChemMedChem. 2024 Feb 26:e202300480. doi: 10.1002/cmdc.202300480. Online ahead of print.ABSTRACTAmphipathicity is a critical characteristic of helical antimicrobial peptides (AMPs). The hydrophilic region, primarily composed of cationic residues, plays a pivotal role in the initial binding to negatively charged components on bacterial membranes through electrostatic interactions. Subsequently, the hydrophobic region interacts with hydrophobic components, inducing membrane perturbation, ultimately leading to cell death, or inhibiting intracellular function. Due to the extensive diversity of natural and synthetic AMPs with r...
Source: ChemMedChem - February 26, 2024 Category: Chemistry Authors: Hai Bui Thi Phuong Hoa Doan Ngan Binh Le Huy Hoang Vu Dinh Huy Luong Xuan Source Type: research

The amphipathic design in helical antimicrobial peptides
ChemMedChem. 2024 Feb 26:e202300480. doi: 10.1002/cmdc.202300480. Online ahead of print.ABSTRACTAmphipathicity is a critical characteristic of helical antimicrobial peptides (AMPs). The hydrophilic region, primarily composed of cationic residues, plays a pivotal role in the initial binding to negatively charged components on bacterial membranes through electrostatic interactions. Subsequently, the hydrophobic region interacts with hydrophobic components, inducing membrane perturbation, ultimately leading to cell death, or inhibiting intracellular function. Due to the extensive diversity of natural and synthetic AMPs with r...
Source: ChemMedChem - February 26, 2024 Category: Chemistry Authors: Hai Bui Thi Phuong Hoa Doan Ngan Binh Le Huy Hoang Vu Dinh Huy Luong Xuan Source Type: research

Small Molecule-Drug Conjugates: Opportunities for The Development of Targeted Anticancer Drugs
ChemMedChem. 2024 Feb 23:e202300720. doi: 10.1002/cmdc.202300720. Online ahead of print.ABSTRACTConventional chemotherapy is insufficient for precise cancer treatment due to its lack of selectivity and inevitable side effects. Targeted drugs have emerged as a promising solution for precise cancer treatment. A common strategy is to conjugate therapeutic agents with ligands that can specifically bind to tumor cells, providing targeted therapy. Similar to the more successful antibody drug conjugates (ADCs), small molecule drug conjugates (SMDCs) are another promising class of targeted drugs, consisting of three parts: targeti...
Source: ChemMedChem - February 24, 2024 Category: Chemistry Authors: Jingjing Zhang Fanchun Hu Omer Aras Yichao Chai Feifei An Source Type: research