Current Pharmaceutical Design - Volume 31, Issue 14, 2025
Volume 31, Issue 14, 2025
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Exploring the Therapeutic Potential of Natural Plants in Modulating Molecular and Cellular Pathways Involved in Diabetic Neuropathy: Mechanism and Biochemical Evaluation
Authors: Zeeshan Ali and Uma BhandariDiabetic neuropathy (DN) is a widespread and severely debilitating consequence of diabetes mellitus that impairs function, causes discomfort, and damages peripheral nerves. Numerous molecular pathways are involved in the pathogenesis of DN, including cyclooxygenase, polyol, protein kinase C, and inflammatory pathways. These molecular pathways may be responsible for the mechanism behind the onset and development of DN. The metabolic profile can be evaluated by examining the molecular mechanisms that connect diabetes to certain biochemical indicators. Historically, the use of plants and herbs as medicine has been highly valued in many populations. These traditional sources, either alone or in combination with contemporary drugs, are being studied by modern medicine for their potential applications in managing and treating diabetic neuropathy. The efficacy and potential negative effects of an herb are largely dependent on its purity and provenance. Rich supplies of bioactive chemicals with particular pharmacological qualities that don't have negative side effects can be found in many plants. Some phytoconstituents with antidiabetic properties are found in medicinal plants, including terpenoids, saponins, flavonoids or carotenoids, alkaloids, and glycosides. We conclude with the statement that developing novel therapeutic procedures for the therapy of DN would be aided by the effective manipulation of common molecular pathways.
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Pyrimidine: A Privileged Scaffold for the Development of Anticancer Agents as Protein Kinase Inhibitors (Recent Update)
Authors: Mai M. Zeid, Osama M. El-Badry, Salwa El-Meligie and Rasha A. HassanThe pyrimidine nucleus is a fundamental component of human DNA and RNA, as well as the backbone of many therapeutic agents. Its significance in medicinal chemistry is well-established, with pyrimidine derivatives receiving considerable attention due to their potent anticancer properties across various cancer cell lines. Numerous derivatives have been synthesized, drawing structural inspiration from known anticancer agents like dihydropyrimidine compounds, which include the active cores of drugs such as 5-fluorouracil and monastrol, both of which have demonstrated strong anticancer efficacy. Additionally, various pyrimidine derivatives have been developed through different synthetic pathways, exhibiting promising anticancer potential. In response to the growing need for effective cancer treatments, recent efforts have focused on synthesizing and exploring novel pyrimidine derivatives with improved efficacy and specificity. This review aims to highlight the versatility of pyrimidine-based compounds in cancer therapy, emphasizing not only their potency and binding affinity but also their optimal interaction with diverse biological targets. The goal is to facilitate the design of new pyrimidine derivatives with enhanced anticancer potential, providing effective solutions for the treatment of various cancer types.
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Decoding Epilepsy: Prickle2 and Multifaceted Molecular Pathway Connections
Authors: Yuhang Liu, Fan Peng, Jie Shu, Xiaolan Li and Chengfu YuanBackgroundThe Prickle2 (Pk2) gene shows promising potential in uncovering the underlying causes of epilepsy, a neurological disorder that is currently not well understood. This paper utilizes the online tool PubMed to gather and condense information on the involvement of PCP channels and the associated roles of PCP pathway molecules in the onset of epilepsy. These findings are significant for advancing epilepsy treatment. Additionally, the paper discusses future directions for clinical trials and outlines potential therapeutic targets.
MethodsThis review systematically analyzes the biological functions and mechanisms of the Prickle2 gene in epilepsy. Studies were retrieved from PubMed using keywords such as “Prickle2”, “epilepsy”, and “PCP pathway”, focusing on research published between 2000 and 2023 in English. Inclusion criteria included original studies and reviews on Prickle2's role in epilepsy. Studies unrelated to these topics or lacking sufficient data were excluded. Key data on Prickle2's functions and its link to epilepsy were extracted, and findings were summarized after a quality assessment of the literature.
ResultsAlthough there are currently conflicting results regarding the possibility that Prickle2 may cause epilepsy in different organisms, we believe that as more cases involving Prickle2 mutations are reported and more related animal experiments are conducted, the findings will become clearer.
ConclusionDue to the biological functions and mechanisms associated with the Prickle2 protein, it may serve as a useful biomarker or potential therapeutic target for epilepsy treatment.
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Exploration of Novel Therapeutic Targets for Breast Carcinoma and Molecular Docking Studies of Anticancer Compound Libraries with Cyclin-dependent Kinase 4/6 (CDK4/6): A Comprehensive Study of Signalling Pathways for Drug Repurposing
By Asim NajmiAimsThis study aims to identify and evaluate promising therapeutic proteins and compounds for breast cancer treatment through a comprehensive database search and molecular docking analysis.
BackgroundBreast cancer (BC), primarily originating from the terminal ductal-lobular unit of the breast, is the most prevalent form of cancer globally. In 2020, an estimated 2.3 million new cases were reported, resulting in approximately 685,000 deaths. Mutations in the BRCA1 and BRCA2 genes are well-established in hereditary breast cancer. The identification of effective therapeutic proteins for BC remains a complex and evolving area of research.
ObjectiveThis study aims to identify and evaluate promising therapeutic proteins and compounds specific to breast cancer through a comprehensive database search and molecular docking analysis.
MethodsA rigorous search was conducted within the National Cancer Institute (NCI), NCI Metathesaurus, SIGnaling Network Open Resource (SIGNOR), Human Protein Atlas (HPA), and the Human Phenotype Ontology (HPO) to shortlist proteins linked to BC (CUI C0678222). Recent studies were reviewed to understand the administration of CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) combined with endocrine therapy for HR-positive and HER2-negative breast cancer. Anticancer compound libraries available at ZINC and PubChem were analyzed. Compounds were evaluated based on their binding energies with CDK4 protein, a rationally selected druggable target.
ResultsKey proteins linked to breast cancer were identified through database searches. Proliferation, apoptosis, and G1/S transition pathways were frequently found dysregulated in breast cancer. ZINC13152284 exhibited the strongest binding energy at -10.9 Kcal/mol, followed by ZINC05492794 with a binding energy of-10.4 Kcal/mol. Preexisting drugs showed lower binding energies with the CDK4 protein.
ConclusionThe study highlights the importance of drug repurposing as a strategy for the safe and effective treatment of breast cancer. Synthetic inhibitors often cause severe side effects, emphasizing the need for novel targets and compounds with better therapeutic profiles. Molecular docking identified promising compounds from the ZINC database, suggesting potential new avenues for breast cancer therapy.
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Volumes & issues
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Volume 31 (2025)
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Volume (2025)
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Volume 30 (2024)
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Volume 29 (2023)
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Volume 28 (2022)
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Volume 27 (2021)
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Volume 26 (2020)
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Volume 25 (2019)
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Volume 24 (2018)
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Volume 23 (2017)
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Volume 22 (2016)
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Volume 21 (2015)
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Volume 20 (2014)
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Volume 19 (2013)
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Volume 18 (2012)
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Volume 17 (2011)
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Volume 16 (2010)
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Volume 15 (2009)
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Volume 14 (2008)
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Volume 13 (2007)
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Volume 12 (2006)
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Volume 11 (2005)
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Volume 10 (2004)
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Volume 9 (2003)
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Volume 8 (2002)
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Volume 7 (2001)
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Volume 6 (2000)
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