Current Topics in Medicinal Chemistry - Volume 25, Issue 22, 2025
Volume 25, Issue 22, 2025
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The Applications of Computational Tools in PROTAC Development
More LessAuthors: Wangqiu He, Kejia Yan, Zhou Chen, Lianhua Piao, Shan Chang and Ren KongThe increasing importance of PROTACs (proteolysis-targeting chimeras) has attracted significant attention from both the academic community and industry. PROTACs are hetero-bifunctional small molecules that can bind to both the protein of interest (POI) and the E3 ubiquitin ligase (E3), inducing ubiquitinated degradation of POI. The unique mechanisms of PROTACs, such as event-driven pharmacology and modulation of protein degradation, provide novel therapeutic modalities for various diseases, including oncology, antiviral therapies, neurodegenerative diseases, acne, and others. Numerous computational methods, including structural prediction, molecular generation, and molecular dynamics simulation, have been applied in the development of PROTAC molecules. This review introduces the fundamental principles of computational tools used in PROTAC design, as well as typical examples validated by experiments.
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Common Signaling Pathways in Cancer and Alzheimer's Disease May Point to New Treatments
More LessAuthors: Chenglong Wu, Leyao Jiang, Ying Zhong and Zongliang LiuCancer and Alzheimer's disease (AD) are among the most prevalent diseases in contemporary society, exerting profound psychological and physical distress on affected individuals and their kin. There is an emerging consensus from epidemiological studies suggesting a potential inverse relationship between the two conditions; that is, the presence of one disease might offer some level of protection against the other. The etiology of both cancer and AD is intricately linked to dysregulation and perturbations in critical signaling pathways. These pathways, along with the diverse factors they encompass, exert distinct influences on the pathogenesis of two diseases. In this paper, we make a short review of the different mutations in the relevant signaling pathways between cancer and AD and introduce a few representative drugs for the two diseases based on various targets to provide a new idea for treating cancer and AD.
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Elucidating the Pivotal Neuroprotective Mechanisms and Therapeutic Variants of Erythropoietin in Neonatal Brain Injury
More LessNeonatal brain injury (NBI) encompasses a variety of neurological acquired conditions affecting newborns. These conditions include hypoxia-ischemia, hyperoxic, periventricular leukomalacia, intrauterine infection, as well as perinatal cerebral hemorrhage. Each year, thousands of babies are born with signs of brain injury. It is estimated that two-thirds of these newborn infants with brain injury would either die or survive with mild to severe neurologic sequelae, largely due to the absence of no widely accepted treatment methods. Erythropoietin (Epo) is a humoral intermediary associated with the maturation as well as the proliferation of erythroid progenitor cells. Systematic administration of Epo triggers the elevation of Epo levels in cerebrospinal fluid (CSF) extracts, which means that Epo is capable of crossing the blood-brain barrier into the CSF. It has been reported that Epo treatment enhances the brain's network connectivity, improving local information transmission and promoting a shift toward a more integrated and consistent network architecture. This, in turn, augments both local and global connectivity efficiency. Exogenous Epo was found to be capable of regulating neurogenesis. Moreover, Epo was also reported to be associated with the inhibition of demyelination of axons, as well as the production of myelin-derived inhibitory proteins, which are inhibitory factors involved in axonal extension. Administration of recombinant human erythropoietin in neonatal rats provided neuroprotection against hyperoxia-induced oxidative stress. Furthermore, Epo administration during the neonatal period was shown to reverse molecular alterations associated with impaired development of the potassium-chloride co-transporter isoform 2 (KCC2), as well as deficits related to preterm birth during the postnatal period. Moreover, Epo was capable of blocking microglial stimulation, decreasing phagocytosis in vitro, as well as inhibiting the generation of inflammatory cytokines in vitro as well as in vivo. Thus, Epo via EpoR is able to influence brain connectivity, synaptogenesis, neurite repair, oxygen-induced brain injury, potassium chloride co-transporters, and inflammation via key signaling pathways to induce therapeutic as well as neuroprotection in NBI. Thus, Epo is a very promising neuroprotective as well as a therapeutic agent in the treatment of NBI. This review aimed to explore the neuroprotective and therapeutic mechanisms of Epo in NBI, as well as the potential of Epo variants.
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The Impact and Role of Artificial Intelligence (AI) in Healthcare: Systematic Review
More LessAuthors: Kavya Singh, Ashish Prabhu and Navjeet KaurIntroductionHealthcare organizations are complicated and demanding for all stakeholders, but artificial intelligence (AI) has revolutionized several sectors, especially healthcare, with the potential to enhance patient outcomes and standard of life. Quick advancements in AI can transform healthcare by implementing it into clinical procedures. Reporting AI's involvement in clinical settings is vital for its successful adoption by providing medical professionals with the necessary information and tools.
BackgroundThis paper offers a thorough and up-to-date summary of the present condition of AI in medical settings, including its possible uses in patient interaction, treatment suggestions, and disease diagnosis. It also addresses the challenges and limitations, including the necessity for human expertise along with future directions. In doing so, it improves the understanding of AI's relevance in healthcare and supports medical institutions in successfully implementing AI technologies.
MethodsThe structured literature review, with its dependable and reproducible research process, allowed the authors to acquire 337 peer-reviewed publications from indexing databases, such as Scopus and EMBASE, without any time restrictions. The researchers utilized both qualitative and quantitative factors to assess authors, publications, keywords, and collaboration networks.
ResultsAI implementation in healthcare holds enormous potential for enhancing patient outcomes, treatment recommendations, and disease diagnosis. AI technologies can use massive datasets and recognize patterns to beat human performance in various healthcare domains. AI provides improved accuracy, reduced expenses, and time savings. It can transform customized medicine, optimize drug dosages, improve management of population health, set guidelines, offer digital medical assistants, promote mental health services, boost patient knowledge, and maintain patient-clinician trust.
ConclusionAI can be utilized to detect diseases, develop customized therapy plans, and support medical professionals with their clinical decision-making. Instead of just automating jobs, AI focuses on creating technologies that can improve patient care in several healthcare settings. However, challenges such as biasness, data confidentiality, and data quality must be resolved for the appropriate and successful integration of AI in healthcare.
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Multimodal Activity of a Novel Compound against Prostate and Pancreatic Cancer
More LessAuthors: Flaviana Alves dos Santos, Joelson Germano Crispim, Eduardo Davi Lima da Silva, Arsênio Rodrigues Oliveira, Aldilane Gonçalves da Fonseca, Telma Maria Araújo Moura Lemos, Ana Cristina Lima Leite, Michelle Melgarejo da Rosa, Maira Galdino da Rocha Pitta, Michelly Cristiny Pereira, Ivan da Rocha Pitta and Moacyr Jesus Barreto de Melo RêgoBackgroundProstate and pancreatic cancers pose significant global health challenges. This study explored the potential of compound 5b, a novel phthalimido-1,3-thiazole derivative, as an anticancer agent against these malignancies.
MethodsIn vitro, compound 5b exhibited potent cytotoxic activity against both prostate (DU-145 and PC-3) and pancreatic (Panc-1 and Mia Paca-2) cancer cell lines. Notably, it significantly reduced colony formation in PC-3 cells, potentially hindering tumor growth. Furthermore, treatment with compound 5b suppressed cell migration and induced cell cycle arrest in the PC-3 line. Additionally, it triggered cell death through late apoptosis and necrosis at higher concentrations. Safety evaluations in mice revealed no mortality or adverse effects after a 30-day treatment with compound 5b. Key blood parameters (hematology) and biochemical markers of liver and kidney function remained unaltered.
ResultsCompound 5b significantly reduced colony formation, suppressed cell migration, and induced cell cycle arrest and apoptosis/necrosis in prostate cancer cells. In vivo, safety evaluations showed no adverse effects in treated mice, with blood and biochemical markers remaining normal.
ConclusionThese findings suggest that compound 5b holds promise for further development as a therapeutic option for prostate and pancreatic cancers. Its multimodal activity profile, targeting cell viability, migration, cell cycle progression, and cell death, warrants further investigation.
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Chemical Profiling and Antibacterial Potential of Methanol Extract of Solanum xanthocarpum Fruits against Methicillin-Resistant Staphylococcus aureus: Implications for AMR Management
More LessAimTo investigate the antimicrobial potential of methanol fruit extract of Solanum xanthocarpum against Methicillin-Resistant Staphylococcus aureus (MRSA) and elucidate its mode of action.
BackgroundThe rise of antimicrobial resistance (AMR) demands the exploration of alternative therapeutic strategies to combat resistant pathogens.
ObjectiveTo evaluate the efficacy of Solanum xanthocarpum methanol extract against MRSA, and identify its active constituents and mechanism of action.
MethodsThe fruits of Solanum xanthocarpum were extracted using various solvents, with hexane and methanol yielding the highest results. Microbroth dilution assays assessed antimicrobial activity, while in vitro assays such as Alamar blue, Scanning Electron Microscopy (SEM), protein, and nucleic acid leakage examined metabolic disruption and cell membrane integrity. Gas Chromatography-Mass Spectrometry (GC-MS) was used to identify active compounds, and molecular docking studies assessed interactions with key MRSA proteins.
ResultsThe methanol extract demonstrated significant antimicrobial activity against MRSA, causing metabolic disruption and leakage of cellular contents as evidenced by various in vitro assays including alarm blue, SEM, and protein and nucleic acid leakage assay. GC-MS analysis identified alpha-linoleic acid and palmitic acid as key active components. Molecular docking studies confirmed their inhibition of beta-lactamase activity, cell wall biosynthesis, efflux pumps, and virulence factors.
ConclusionThe findings suggest that Solanum xanthocarpum methanol fruit extract has promising potential as a natural remedy against AMR associated with MRSA.
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Volumes & issues
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Volume 25 (2025)
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Volume 23 (2023)
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Volume 22 (2022)
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Volume 21 (2021)
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Volume 19 (2019)
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Volume 7 (2007)
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Volume 5 (2005)
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Volume 4 (2004)
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Volume 3 (2003)
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Volume 2 (2002)
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Volume 1 (2001)
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