Mini reviews in medicinal chemistry最新文献

{"title":"Progress in Heterocyclic Hybrids for Breast Cancer Therapy: Emerging Trends, Hybridization Techniques, Mechanistic Pathways and SAR Insights.","authors":"Akhilesh Gangwar, Agnidipta Das, Vikas Jaitak","doi":"10.2174/0113895575386481250811052953","DOIUrl":"https://doi.org/10.2174/0113895575386481250811052953","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer is a widespread and life-threatening disease. While FDAapproved anti-BC drugs have improved survival rates, issues like drug resistance and adverse effects highlight the need for new therapeutic options. Molecular hybridization, a modern drug discovery strategy, combines different pharmacophores or frameworks into a single molecule to enhance pharmacological activity and improve treatment outcomes. Hybridizing two or more heterocyclic moieties has become a promising approach in anti-cancer drug discovery.</p><p><strong>Methods: </strong>This article reviews the role of heterocyclic hybrids in BC therapy, based on literature from 1995 to 2024 available in PubMed. Key heterocyclic hybrids, pyrimidine, triazole, indole, coumarin, beta-carboline, azepine, isoquinoline, benzoxepine, and platinum-core hybrids were included.</p><p><strong>Results: </strong>Triazole, in particular, was found to be a highly effective scaffold for BC treatment when combined with indole, pyridazinone, and steroid pharmacophores.</p><p><strong>Discussion: </strong>The article discusses novel molecular hybridization strategies, current BC treatment options, clinical studies, key functional groups, anti-apoptotic mechanisms, and protein-ligand interactions. Structure-activity relationships are explored to highlight desirable pharmacophoric features, aiding in the development of more effective BC therapies.</p><p><strong>Conclusion: </strong>Each heterocyclic hybrid class of BC comprises some salient features and potentials, which may be further investigated to obtain novel effective heterocyclic hybrid molecules in BC therapy.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in the Therapeutic Prospective of Heterocyclic Derivatives as COX-2 Inhibitors (2019-Present).","authors":"Afaf Y Khormi, Amani M R Alsaedi, Thoraya A Farghaly, Dina H Dawood","doi":"10.2174/0113895575385764250711091807","DOIUrl":"https://doi.org/10.2174/0113895575385764250711091807","url":null,"abstract":"<p><p>Inflammation is a key contributor to the pathophysiology of various chronic diseases, including cancer, arthritis, cardiovascular disorders, chronic wounds, and gastrointestinal conditions, many of which rank among the leading causes of mortality worldwide, according to the WHO. The prevalence of chronic inflammation-related diseases is projected to rise steadily over the next 30 years, with an estimated three out of five individuals dying daily as a result of such conditions. Consequently, there is a growing demand for the discovery of novel anti-inflammatory agents. Cyclooxygenases play a pivotal role in inflammatory processes, being responsible for the synthesis of prostaglandins. COX-1 is constitutively expressed and primarily associated with \"housekeeping\" physiological functions, whereas COX-2 is an inducible isoform involved in inflammatory responses. Due to its role in inflammation and relatively favorable gastric safety profile compared to traditional NSAIDs, COX-2 has emerged as a significant therapeutic target for inflammation-related disorders. However, the increased risk of stroke and heart attack associated with COX-2 inhibitors has led to the withdrawal of several approved COX-2-targeting drugs from the market. Consequently, the development of new COX-2 inhibitors with potent efficacy and minimal cardiovascular side effects is of critical importance. This review explores a range of oxygen- and nitrogen-containing heterocycles as potential anti-inflammatory agents, emphasizing their COX-2 inhibitory activity, structure-activity relationships, and interactions within the COX-2 active site, as reported in recent studies. The article covers research findings published from 2019 through the first quarter of 2025.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Tetrahydroisoquinoline (THIQ) Scaffold as Therapeutic Modulators of Sigma Receptors.","authors":"Dikshita Lama, A Michael Crider, Marcelo J Nieto","doi":"10.2174/0113895575379843250711134106","DOIUrl":"https://doi.org/10.2174/0113895575379843250711134106","url":null,"abstract":"<p><p>Sigma receptors (σRs), comprising σ1 and σ2 subtypes, are versatile pharmacological targets with significant roles in cancer, neurodegeneration, and psychiatric disorders. The tetrahydroisoquinoline (THIQ) scaffold, a core structure in many biologically active compounds, has garnered attention as a versatile platform for designing σRs ligands. THIQ-based compounds exhibit potent σRs binding affinity, leading to therapeutic effects ranging from neuroprotection to antitumor activity. This mini-review explores the structural features of THIQ ligands, their interaction with σRs, and their therapeutic implications. Challenges and future prospects for THIQ derivatives in σRs research are also discussed.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-Property Relationships Reported for the New Drugs Approved in 2024.","authors":"Kihang Choi","doi":"10.2174/0113895575390155250711072709","DOIUrl":"https://doi.org/10.2174/0113895575390155250711072709","url":null,"abstract":"<p><p>This mini-review summarizes the structure-property relationships of seven smallmolecule drugs approved in 2024, providing insights into effective lead-to-candidate optimization strategies. The analysis focused on aprocitentan, flurpiridaz F-18, inavolisib, vorasidenib, ensitrelvir, golidocitinib, and zorifertinib, highlighting the key structural modifications that enhanced their drug-like properties. Notable optimization strategies included the strategic use of five- and sixmembered nitrogen-containing heterocycles as cyclic bioisosteres and solubilizing groups. For the kinase inhibitor golidocitinib, the unique position of a solubilizing group within the binding pocket achieved dual benefits, i.e., enhanced target selectivity and physicochemical properties. When developing central nervous system-penetrant drugs such as zorifertinib, careful control of rotatable bonds, hydrogen bond donors, and molecular lipophilicity was critical for optimizing blood-brain barrier penetration while remaining suitable for oral administration. These findings on structureproperty relationships offer valuable guidance for future drug development, particularly in addressing challenges related to solubility, bioavailability, and tissue-specific drug distribution.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emblica officinalis Gaertn. Fruits, their Phytochemicals, and Composite Herbal Products as Adjuncts in Preventing Ionizing Radiation Effects: Possible Use in Clinics.","authors":"Manjeshwar Shrinath Baliga","doi":"10.2174/0113895575362233250429114954","DOIUrl":"https://doi.org/10.2174/0113895575362233250429114954","url":null,"abstract":"<p><p>In the management of solid tumors, ionizing radiation is a critical therapeutic modality, particularly when surgical intervention is impractical due to patient-related factors, such as compromised health or elevated mortality risk. However, its non-selective action can cause serious side effects that negate the therapeutic benefits. Efforts have thus been made to identify pharmacological agents that can selectively protect normal tissues from exposure to ionizing radiation. Seven decades of study, however, have shown that the desired success has not been achieved in obtaining an ideal radioprotective agent. Moreover, even at optimal doses, the FDA-approved drug, amifostine (also known as WR-2721 [S-2- (3-aminopropyl-amino) ethyl phosphorothioic acid], exhibits significant toxicity. An ideal radioprotective agent can also be beneficial in environments where individuals are exposed to prolonged, low-dose radiation. Considering this, there is a pressing need to develop methods of shielding cells and patients from the deleterious effects of radiation, and a non-toxic radioprotective drug can be useful in both clinical and occupational contexts. Studies have shown that the fruits of Emblica officinalis and its cardinal phytochemicals, such as gallic acid, ellagic acid, quercetin, geraniin, corilagin, and kaempferol, have been demonstrated to mitigate radiationinduced side effects. Research has also demonstrated that fruits can reduce the severity of radiationinduced mucositis in head and neck cancer patients undergoing curative treatment. Currently, there are no clinically effective non-toxic medications that are beneficial in mitigating radiation-induced ill effects. In lieu of this, for the first time, this review compiles the positive effects of fruits, phytochemicals, and their byproducts, chyawanprash and triphala, on radiation-induced damage, the mechanisms by which these effects occur, and the gaps that must be filled in order for future research to help people and the agricultural and nutraceutical industries.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential of MAO-B Inhibitors with Multi-Target Inhibition and Antioxidant Properties for the Treatment of Neurodegenerative Disorders.","authors":"Moataz A Shaldam, Simone Carradori, Francesco Melfi, Paolo Guglielmi, Francesca Diomede, Maurizio Piattelli, Haytham O Tawfik","doi":"10.2174/0113895575392491250630195630","DOIUrl":"https://doi.org/10.2174/0113895575392491250630195630","url":null,"abstract":"<p><p>Millions of people worldwide are affected by neurodegenerative disorders (NDs), which include a broad range of clinical ailments that affect the brain or peripheral nervous system, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, etc. Neuronal cell death in NDs is often linked to oxidative stress; thus, antioxidant treatment can combat oxidative cell damage, and this strategy has been studied in neurodegenerative processes. Over the past 10 years, we have witnessed intense research activity on the biological potential of human monoamine oxidase (hMAO) inhibitors that have been associated with the prevention of oxidative stress and inflammation. These inhibitors have emerged as promising therapeutic agents, especially in the treatment of neurodegenerative diseases (NDs), where their core activity may help mitigate disease progression. An overview of the current state of numerous scaffolds, such as chromones, coumarins, chalcones, propargylamines, benzothiazoles, aminoisoquinolines, and the natural compounds, including ferulic acid, resveratrol, and chrysin, which combine antioxidant capability and hMAO inhibition is given in this review, with particular attention given to each scaffold's mechanism of action and structure-activity relationships (SARs), which are thoroughly discussed. Focusing on the dual mechanism of action, combining inhibition and antioxidant properties, as a potential therapy for neurodegenerative diseases, we have reviewed the different chemical classes of multi-targetdirected ligand (MTDL) inhibitors developed within this framework. Other central nervous system (CNS)-related enzymes, such as cholinesterases, carbonic anhydrases, and BACE-1, have also been explored as targets in the MTDL strategy. By understanding their biological activity, medicinal chemists can better comprehend biological activity and recommend more effective and specific ND treatments.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Progress of Small-molecule Inhibitors of O-GlcNAcase for Alzheimer's Disease.","authors":"Sheng Sun, JinFa Cao, Shujie Ji, Jian Wang","doi":"10.2174/0113895575376839250606183944","DOIUrl":"10.2174/0113895575376839250606183944","url":null,"abstract":"<p><p>O-GlcNAcylation is a non-canonical form of protein glycosylation that occurs in nuclear, cytoplasmic, and mitochondrial proteins among all multicellular eukaryotes. There are only two enzymes that regulate this post-translational modification, one of which is O-GlcNAcase, a glycoside hydrolase that catalyzes the hydrolytic cleavage of O-GlcNAc from protein substrates. Related studies have shown that the reduction of O-GlcNAc levels is closely related to Alzheimer's disease, which is maintained by reducing the aggregation of tau via inhibiting O-GlcNAcase. Various smallmolecule O-GlcNAcase inhibitors with different chemical structures have been developed and used as chemical probes to explore the O-GlcNAc pathway. Although many reported inhibitors have shown that O-GlcNAcase activity has single-digit nmol IC50 values in binding assays, and molecules, such as LY-3372689, have entered phase II clinical studies, further exploration of novel OGlcNAcase inhibitors with higher inhibitory activity and specificity is still worthy of attention. This article reviews the pathogenesis and therapeutic role of O-GlcNAcase in Alzheimer's disease, as well as the recent progress of O-GlcNAcase small molecule inhibitors, including sugar-derived or non-sugar scaffolds, and summarizes the clinical progress and potential prospects of O-GlcNAcase inhibitors.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topoisomerase II Inhibition in Cancer: A Focus on Metal Complexes.","authors":"Amos Olalekan Akinyemi, Josias da Silveira Rocha, Gabriela Porto de Oliveira, Josenilton de Jesus Santos, Bolaji C Dayo Owoyemi, Fillipe Vieira Rocha","doi":"10.2174/0113895575370547250526062144","DOIUrl":"https://doi.org/10.2174/0113895575370547250526062144","url":null,"abstract":"<p><p>DNA topoisomerases, particularly type II, are crucial for DNA processes, such as replication, transcription, and chromosome segregation, making them prime targets for cancer therapy. This review delves into the multifaceted mechanisms of action of type II topoisomerases, highlighting their essential roles beyond cancer progression. It explores recent advancements in screening and designing metallic complexes as inhibitors of topoisomerase II activity. Emphasizing the structural and functional diversity between alpha and beta isoforms, it elucidates their significance in DNA metabolism and genome integrity. Additionally, this review discusses the interplay of topoisomerase II with cellular components, underscoring its regulatory roles in gene expression. Insights into screening and design strategies for metallic complex inhibitors are provided, showcasing their therapeutic potential against cancer. Overall, this review highlights the importance of understanding topoisomerase II inhibition mechanisms and the versatility of metallic complexes in biomedical research, paving the way for novel therapeutic strategies and broader applications beyond cancer therapy.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Hydrazone Derivatives: Their Sources, Structures, and Bioactivities.","authors":"Hagar Mohamed Mohamed, Hazem G A Hussein, Gamal A Mohamed, Shaimaa G A Mohamed, Sabrin R M Ibrahim","doi":"10.2174/0113895575390008250520114953","DOIUrl":"https://doi.org/10.2174/0113895575390008250520114953","url":null,"abstract":"<p><p>Hydrazone-containing compounds are a diverse group of bioactive compounds known for their unique chemical features and diverse biological activities. Natural hydrazone derivatives have been identified from various natural sources, including bacteria, plants, fungi, and marine organisms. This work provides a comprehensive review of published works on natural hydrazone derivatives, including their sources, structural features, and biological activity in the period from 1967 to March 2025. In this work, 72 compounds were reviewed, along with 75 references being cited. The reported findings in this work highlight the therapeutic potential of these compounds in pharmaceutical research and drug discovery.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovations in Cannabis Delivery Systems: A Patent Review (2012-2024).","authors":"Ana Sofía Guerrero Casas, Vanessa Castro Felix Lima, Nicolas Redondo, Izabel Almeida Alves, Diana Marcela Aragón","doi":"10.2174/0113895575343984250519051357","DOIUrl":"https://doi.org/10.2174/0113895575343984250519051357","url":null,"abstract":"<p><strong>Introduction: </strong>Cannabis sativa has been cultivated for over 11,700 years, originating in Central and Southeast Asia, and has been used for medical, recreational, and religious purposes. Among its therapeutic potentials, it is notable for its capacity to alleviate pain, nausea, anxiety, and more. The plant's primary secondary metabolites are cannabinoids, which interact with the endocannabinoid system to produce these effects. However, due to the dosage variability and the secondary effects associated with a lack of targeted action, their medical use is limited, creating the need for effective delivery systems.</p><p><strong>Methodology: </strong>This systematic patent review on cannabis drug delivery systems was conducted using patents retrieved from the Espacenet database. The search employed the keywords \"Cannabis\" and \"Delivery,\" along with the IPC classification code A61, to filter patents filed between 2012 and 2024. This initial search yielded 99 patents, which were further screened to identify 15 patents that met the inclusion criteria.</p><p><strong>Results: </strong>Of the selected patents, most originated from the United States, followed by Canada, international patents (WIPO), and China. A notable increase in patent filings occurred in 2022, coinciding with the peak in scientific publications on the topic. This trend indicates a growing interest in the design of cannabis delivery systems.</p><p><strong>Discussion: </strong>The historical importance and therapeutic potential of Cannabis sativa are welldocumented, yet modern medical use remains restricted due to pharmacokinetic limitations. Delivery systems such as extracellular vesicles, microneedles, and emulsions have been developed to improve the bioavailability and stability of cannabinoids. Extracellular vesicles facilitate targeted, noninvasive delivery of cannabinoids to the central nervous system. Microneedles offer a painless method for transdermal administration, overcoming skin barrier limitations. Emulsions improve the solubility and bioavailability of lipophilic cannabinoids, making them suitable for various administration routes.</p><p><strong>Conclusion: </strong>Since 2012, there has been considerable growth in patents and publications related to cannabis drug delivery systems, driven by the therapeutic potential of cannabinoids. Innovations in delivery systems like emulsions, microneedles, and extracellular vesicles aim to improve the pharmacokinetics and therapeutic efficacy of cannabis-derived compounds, representing a shift towards medical cannabis applications.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}