Article
Chemistry, Medicinal
Eleni Kaisis, Laura J. J. Thei, Gary J. J. Stephens, Mark L. L. Dallas
Summary: Cav2.2 channels are modulated by Ab(1-42) peptides, and this modulation has different effects at different concentrations. This study reveals a potential mechanistic link between amyloid accumulation and Cav2.2 channel modulation.
Review
Pharmacology & Pharmacy
Ludovica Filippini, Nadine J. J. Ortner, Teresa Kaserer, Jorg Striessnig
Summary: Voltage-gated L-type Ca2+-channels, especially Ca(v)1.3 subtype, are potential drug targets for the treatment of various diseases. However, the selectivity of Ca(v)1.3-selective blockers remains controversial, and there are no suitable pharmacological tools to confirm or refute the role of Ca(v)1.3 channels in cellular responses. Essential criteria for a small molecule to be considered Ca(v)1.3-selective are suggested.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Liqiong Ding, Ping Jiang, Xinfeng Xu, Wanzhen Lu, Chan Yang, Lin Li, Pingzheng Zhou, Shuwen Liu
Summary: The study identified T-type calcium channel blockers as potential inhibitors of HSV-2 infection, while L-type calcium channel blockers showed no significant effect. Additionally, benidipine exerted antiviral effects by suppressing viral gene expression in the late stage of infection.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Paz Duran, Santiago Loya-Lopez, Dongzhi Ran, Cheng Tang, Aida Calderon-Rivera, Kimberly Gomez, Harrison J. Stratton, Sun Huang, Ya-ming Xu, E. M. Kithsiri Wijeratne, Samantha Perez-Miller, Zhiming Shan, Song Cai, Anna T. Gabrielsen, Angie Dorame, Kyleigh A. Masterson, Omar Alsbiei, Cynthia L. Madura, Guoqin Luo, Aubin Moutal, John Streicher, Gerald W. Zamponi, A. A. Leslie Gunatilaka, Rajesh Khanna
Summary: This study identified argentatin C, a compound derived from the Native American medicinal plant Parthenium incanum, which can block the activity of voltage-gated sodium and calcium channels and has potential as a novel treatment for painful conditions. Experimental results demonstrated that argentatin C decreased ion currents and excitability in sensory neurons and relieved postsurgical pain in a mouse model. Therefore, argentatin C may serve as an alternative therapy for chronic pain management.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Chemistry, Physical
Mehdi Yoosefian, Batool Tajaddini, Saeid Ahmadzadeh, Maryam Zeraati-Moghani, Zahra Pakdin-Parizi
Summary: Drinking excessive alcohol can cause chronic diseases and serious problems such as heart disease, high blood pressure, stroke, digestive problems, and liver disease. A molecular dynamics simulation study found that ethanol blocks calcium channels and interferes with calcium ion passage. Furthermore, calcium ions have a greater tendency to interact with residues inside the protein channel in the presence of ethanol.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Medicine, General & Internal
Kai-Feng Shen, Xiao-Lin Yang, Guo-Long Liu, Gang Zhu, Zhong-Ke Wang, Xian-Jun Shi, Ting-Ting Wang, Zhi-Feng Wu, Sheng-Qing Lv, Shi-Yong Liu, Hui Yang, Chun-Qing Zhang
Summary: The study revealed that ClC-mediated current was increased in the hippocampal neurons of chronic TLE mice. Application of chloride channel blockers NPPB and DIDS reduced the current and increased inhibitory synaptic transmission in TLE mice. These drugs also decreased seizure frequency and the average power of ictal high-frequency oscillations in TLE mice.
Review
Pharmacology & Pharmacy
Siddesh Kelkar, Namrata Nailwal, Nirav Yogesh Bhatia, Gaurav Doshi, Sadhana Sathaye, Angel Pavalu Godad
Summary: Inflammation is a mechanism of the body to activate the immune system and prevent bacteria and viruses from causing toxic effects. Voltage-gated ion channel blockers can be an important alternative to deal with the side effects of current drugs.
CURRENT DRUG TARGETS
(2022)
Review
Cell Biology
Flavia Tasmin Techera Antunes, Alessandra Hubner De Souza, Juliana Figueira, Nancy Scardua Binda, Vanice Paula Ricardo Carvalho, Luciene Bruno Vieira, Marcus Vinicius Gomez
Summary: Calcium channels play important roles in the central nervous system, regulating critical processes such as membrane excitability and neurotransmission. In particular, N-type calcium channels have been implicated in pain, inflammation, and excitotoxicity, and are targeted by certain therapeutic strategies. This review focuses on the role of N-type calcium channels in neurological disorders such as Huntington's disease, multiple sclerosis, and migraine, and discusses potential therapeutic strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Yangmei Li, Chao Chang, Zhi Zhu, Lan Sun, Chunhai Fan
Summary: The dysfunction of voltage-gated calcium channels leading to a deficiency in Ca2+ fluxes is associated with calcium channelopathies such as epilepsy and periodic paralysis. By using resonant terahertz waves, researchers have demonstrated enhanced selectivity and conductance of Ca2+, potentially offering therapeutic interventions in correcting calcium channel deficiencies and inducing apoptosis in tumor cells.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemical Research Methods
G. M. Archana, R. C. Arunkumar, R. V. Omkumar
Summary: This study reports the presence of L-type VGCC subunit proteins in HEK-293 cells and develops simple methods for its assay. The activity of L-VGCC in HEK-293 cells can be detected through endogenous expression, eliminating the need for transfection. Different experimental methods were used to detect the activity, and the antagonist nifedipine was found to block the activity. These findings offer commercially viable assays for drug screening.
ANALYTICAL BIOCHEMISTRY
(2022)
Article
Biology
Anita Siller, Nadja T. Hofer, Giulia Tomagra, Nicole Burkert, Simon Hess, Julia Benkert, Aisylu Gaifullina, Desiree Spaich, Johanna Duda, Christina Poetschke, Kristina Vilusic, Eva Maria Fritz, Toni Schneider, Peter Kloppenburg, Birgit Liss, Valentina Carabelli, Emilio Carbone, Nadine Jasmin Ortner, Joerg Striessnig
Summary: In Parkinson's disease, Cav2.3 R-type Ca2+ currents play a significant role in dopaminergic Substantia nigra neurons. The membrane-anchored beta 2 splice variants beta 2a and beta 2e are crucial for stabilizing Cav2.3 gating properties and enhancing Ca2+ currents. These findings were confirmed in mouse models.
Article
Neurosciences
Eric A. Bancroft, Martha De La Mora, Gauri Pandey, Sara M. Zarate, Rahul Srinivasan
Summary: Parkinson's disease is associated with increased levels of S100B and its overexpression accelerates the loss of dopaminergic neurons. The study found that S100B can alter the activity of dopamine neurons, providing important insights into the pathophysiology of early Parkinson's disease.
Article
Cell Biology
Yiliam Cruz-Garcia, Katalin Barkovits, Michael Kohlhaas, Simone Pickel, Michelle Gulentz, Cornelia Heindl, Kathy Pfeiffer, Petra Eder-Negrin, Christoph Maack, Katrin Marcus, Michaela Kuhn, Erick Miranda-Laferte
Summary: Ca2+ influx through LTCCs in cardiomyocytes plays a crucial role in regulating Ca2+-dependent processes. In this study, proximity labeling and quantitative proteomics were used to identify proteins associated with Ca-v beta(2) in cardiomyocytes. These proteins are involved in diverse cellular functions. Additionally, interaction between Ca-v beta(2) and RyR2 was found to be necessary for the Ca2+-induced Ca2+ release mechanism in cardiomyocytes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Denis P. Laryushkin, Sergei A. Maiorov, Valery P. Zinchenko, Sergei G. Gaidin, Artem M. Kosenkov
Summary: The study demonstrates that blockade of L-type VGCC can reduce the half-width and amplitude of bicuculline-induced [Ca2+](i) oscillations, decrease the number of PDSs in a cluster, and shorten the cluster duration, while insignificantly affecting the pattern of individual PDSs and the frequency of cluster occurrence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Kajol Shah, Sarah Seeley, Castin Schulz, Jacqueline Fisher, Shubha Gururaja Rao
Summary: Calcium ions are crucial for cell signaling and participate in various physiological functions. Mutations and dysfunctions of calcium channels in the heart can cause diseases and disorders. Drugs targeting calcium channels are used for the treatment of cardiac disorders.
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)