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- Volume 31, Issue 37, 2024
Current Medicinal Chemistry - Volume 31, Issue 37, 2024
Volume 31, Issue 37, 2024
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The Role of the Vagus Nerve in the Microbiome and Digestive System in Relation to Epilepsy
Authors: Carmen Rubio, Ernesto Ochoa, Fernando Gatica, Alonso Portilla, David Vázquez and Moisés Rubio-OsornioThe Enteric Nervous System (ENS) is described as a division of the Peripheral Nervous System (PNS), located within the gut wall and it is formed by two main plexuses: the myenteric plexus (Auerbach's) and the submucosal plexus (Meissner's). The contribution of the ENS to the pathophysiology of various neurological diseases such as Parkinson's or Alzheimer's disease has been described in the literature, while some other studies have found a connection between epilepsy and the gastrointestinal tract. The above could be explained by cholinergic neurons and neurotransmission systems in the myenteric and submucosal plexuses, regulating the vagal excitability effect. It is also understandable, as the discharges arising in the amygdala are transmitted to the intestine through projections the dorsal motor nucleus of the vagus, giving rise to efferent fibers that stimulate the gastrointestinal tract and consequently the symptoms at this level. Therefore, this review's main objective is to argue in favor of the existing relationship of the ENS with the Central Nervous System (CNS) as a facilitator of epileptogenic or ictogenic mechanisms. The gut microbiota also participates in this interaction; however, it depends on many individual factors of each human being. The link between the ENS and the CNS is a poorly studied epileptogenic site with a big impact on one of the most prevalent neurological conditions such as epilepsy.
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Recent Advancements in the Treatment of Alzheimer's Disease: A Multitarget-directed Ligand Approach
Authors: Sumit Kumar, Amol Mahajan, Ramesh Ambatwar and Gopal L. KhatikAlzheimer's disease (AD) is a neurodegenerative disease and one of the leading causes of progressive dementia, affecting 50 million people worldwide. Many pathogenic processes, including amyloid β aggregation, tau hyperphosphorylation, oxidative stress, neuronal death, and deterioration of the function of cholinergic neurons, are associated with its progression. The one-compound-one-target treatment paradigm was unsuccessful in treating AD due to the multifaceted nature of Alzheimer's disease. The recent development of multitarget-directed ligand research has been explored to target the complementary pathways associated with the disease. We aimed to find the key role and progress of MTDLs in treating AD; thus, we searched for the past ten years of literature on “Pub- Med”, “ScienceDirect”, “ACS” and “Bentham Science” using the keywords neurodegenerative diseases, Alzheimer's disease, and multitarget-directed ligands. The literature was further filtered based on the quality of work and relevance to AD. Thus, this review highlights the current advancement and advantages of multitarget-directed ligands over traditional single-targeted drugs and recent progress in their development to treat AD.
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Recent Advances in the Synthesis and Analysis of Atorvastatin and its Intermediates
Authors: Shu-Fang Li, Wei Zhang, Wen Zhang, An Huang, Jia-Qi Zhu, Ya-Jun Wang and Yu-Guo ZhengAtorvastatin, a lipid-lowering drug that is widely used in the treatment of cardiovascular diseases, has significant clinical significance. This article focuses on the synthetic procedures of atorvastatin, including Paal-Knorr synthesis and several new synthetic strategies. It also outlines chemical and chemo-enzymatic methods for synthesizing optically active side chain of atorvastatin. In addition, a comprehensive overview of the analytical monitoring techniques for atorvastatin and its metabolites and impurities is reported, alongside a discussion of their strengths and limitations.
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Exosomal Non-coding RNAs: A New Approach to Melanoma Diagnosis and Therapeutic Strategy
Authors: Jie Liu, Xiaoping Hu, Wenqiang Xin and Xianbin WangMalignant melanoma (MM) is a highly aggressive cancer with a poor prognosis. Currently, although a variety of therapies are available for treating melanoma, MM is still a serious threat to the patient's life due to numerous factors, such as the recurrence of tumors, the emergence of drug resistance, and the lack of effective therapeutic agents. Exosomes are biologically active lipid-bilayer extracellular vesicles secreted by diverse cell types that mediate intercellular signal communication. Studies found that exosomes are involved in cancer by carrying multiple bioactive molecules, including non-coding RNAs (ncRNAs). The ncRNAs have been reported to play an important role in regulating proliferation, angiogenesis, immune regulation, invasion, metastasis, and treatment resistance of tumors. However, the functional role of exosomal ncRNAs in MM remains unknown. Therefore, this review summarizes the current state of melanoma diagnosis, treatment, and the application of exosomal ncRNAs in MM patients, which may provide new insights into the mechanisms involved in melanoma progression and serve as biomarkers for diagnosis and therapeutic targets.
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Biochemistry, Mechanistic Intricacies, and Therapeutic Potential of Antimicrobial Peptides: An Alternative to Traditional Antibiotics
The emergence of drug-resistant strains of pathogens becomes a major obstacle to treating human diseases. Antibiotics and antivirals are in the application for a long time but now these drugs are not much effective anymore against disease-causing drugresistant microbes and gradually it is becoming a serious complication worldwide. The development of new antibiotics cannot be a stable solution to treat drug-resistant strains due to their evolving nature and escaping antibiotics. At this stage, antimicrobial peptides (AMPs) may provide us with novel therapeutic leads against drug-resistant pathogens. Structurally, antimicrobial peptides are mostly α-helical peptide molecules with amphiphilic properties that carry the positive charge (cationic) and belong to host defense peptides. These positively charged AMPs can interact with negatively charged bacterial cell membranes and may cause the alteration in electrochemical potential on bacterial cell membranes and consequently lead to the death of microbial cells. In the present study, we will elaborate on the implication of AMPs in the treatment of various diseases along with their specific structural and functional properties. This review will provide information which assists in the development of new synthetic peptide analogues to natural AMPs. These analogues will eliminate the limitations of natural AMPs like toxicity and severe hemolytic activities.
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LncRNA MEG3: Targeting the Molecular Mechanisms and Pathogenic causes of Metabolic Diseases
Authors: Yiyang Luo, Hailin Wang, Lijun Wang, Wei Wu, Jiale Zhao, Xueqing Li, Ruisi Xiong, Xueliang Ding, Ding Yuan and Chengfu YuanBackground: Non-coding RNA is a type of RNA that does not encode proteins, distributed among rRNA, tRNA, snRNA, snoRNA, microRNA and other RNAs with identified functions, where the Long non-coding RNA (lncRNA) displays a nucleotide length over 200. LncRNAs enable multiple biological processes in the human body, including cancer cell invasion and metastasis, apoptosis, cell autophagy, inflammation, etc. Recently, a growing body of studies has demonstrated the association of lncRNAs with obesity and obesity-induced insulin resistance and NAFLD, where MEG3 is related to glucose metabolism, such as insulin resistance. In addition, MEG3 has been demonstrated in the pathological processes of various cancers, such as mediating inflammation, cardiovascular disease, liver disease and other metabolic diseases. Objective: To explore the regulatory role of lncRNA MEG3 in metabolic diseases. It provides new ideas for clinical treatment or experimental research. Methods: In this paper, in order to obtain enough data, we integrate and analyze the data in the PubMed database. Results: LncRNA MEG3 can regulate many metabolic diseases, such as insulin resistance, NAFLD, inflammation and so on. Conclusion: LncRNA MEG3 has a regulatory role in a variety of metabolic diseases, which are currently difficult to be completely cured, and MEG3 is a potential target for the treatment of these diseases. Here, we review the role of lncRNA MEG3 in mechanisms of action and biological functions in human metabolic diseases.
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Polyphenolic Nano-formulations: A New Avenue against Bacterial Infection
The gradual emergence of new bacterial strains impervious to one or more antibiotics necessitates discovering and applying natural alternatives. Among natural products, various polyphenols exhibit antibacterial activity. However, polyphenols with biocompatible and potent antibacterial characteristics are limited due to low aqueous solubility and bioavailability; therefore, recent studies are considering new polyphenol formulations. Nanoformulations of polyphenols, especially metal nanoparticles, are currently being investigated for their potential antibacterial activity. Nanonization of such products increases their solubility and helps attain a high surface-to-volume ratio and, therefore, a higher reactivity of the nanonized products with better remedial potential than nonnanonized products. Polyphenolic compounds with catechol and pyrogallol moieties efficiently bond with many metal ions, especially Au and Ag. These synergistic effects exhibit antibacterial pro-oxidant ROS generation, membrane damage, and biofilm eradication. This review discusses various nano-delivery systems for considering polyphenols as antibacterial agents.
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In Silico Screening and Molecular Dynamics Simulations against Tyrosine-protein Kinase Fyn Reveal Potential Novel Therapeutic Candidates for Bovine Papillomatosis
Background: Decreased beef productivity due to papillomatosis has led to the development and identification of novel targets and molecules to treat the disease. Protein kinases are promising targets for the design of numerous chemotherapy drugs. Objective: This study aimed to screen and design new inhibitors of bovine Fyn, a protein kinase, using structure-based computational methods, such as molecular docking and molecular dynamics simulation (MDS). Methods: To carry out the molecular docking analysis, five ligands obtained through structural similarity between active compounds along with the cross-inhibition function between the ChEMBL and Drugbank databases were used. Molecular modeling was performed, and the generated models were validated using PROCHECK and Verify 3D. Molecular docking was performed using Autodock Vina. The complexes formed between Fyn and the three best ligands had their stability assessed by MDS. In these simulations, the complexes were stabilized for 100 ns in relation to a pressure of 1 atm, with an average temperature of 300 k and a potential energy of 1,145,336 kJ/m converged in 997 steps. Results: Docking analyses showed that all selected ligands had a high binding affinity with Fyn and presented hydrogen bonds at important active sites. MDS results support the docking results, as the ligand showed similar and stable interactions with amino acids present at the binding site of the protein. In all simulations, sorafenib obtained the best results of interaction with the bovine Fyn. Conclusion: The results highlight the identification of possible bovine Fyn inhibitors; however, further studies are important to confirm these results experimentally.
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Volumes & issues
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Volume 31 (2024)
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Volume 30 (2023)
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Volume 29 (2022)
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Volume 28 (2021)
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Volume 27 (2020)
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Volume 26 (2019)
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Volume 25 (2018)
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Volume 24 (2017)
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Volume 23 (2016)
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Volume 22 (2015)
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Volume 21 (2014)
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Volume 20 (2013)
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Volume 19 (2012)
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Volume 18 (2011)
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Volume 17 (2010)
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Volume 16 (2009)
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Volume 15 (2008)
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Volume 14 (2007)
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Volume 13 (2006)
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Volume 12 (2005)
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Volume 11 (2004)
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Volume 10 (2003)
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Volume 9 (2002)
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Volume 8 (2001)
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Volume 7 (2000)