Medicinal Chemistry最新文献

{"title":"WITHDRAWN: Bismuth(III) Complexes with Schiff Bases: Synthesis, Characterization, Interaction with Biomolecules, Antioxidant and Antimicrobial Activity","authors":"Maxim Y Gvozdev, Natalia V Loginova, Galina A Ksendzova, Nikolai P Osipovich, Tat'yana V Koval'chuk-Rabchinskaya, Yaroslav V Faletrov, Alina M Khodosovskaya, Anatoly N Evtushenkov","doi":"10.2174/1573406419666221118104019","DOIUrl":"10.2174/1573406419666221118104019","url":null,"abstract":"<p><p>Since the authors are not responding to the editor’s requests to fulfill the editorial requirement, therefore, the article has been withdrawn.</p><p><p>Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.</p><p><p>The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php</p><p><strong>Bentham science disclaimer: </strong>It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40700779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the Cytotoxic Effect of Naphthalenacetamides Hydrochlorides on Cervical Cancer-Derived Cells.","authors":"Cristina Martinez-Nava, Cuauhtemoc Perez-Gonzalez, Miguel Ángel Zavala-Sanchez, Erick Cuauhtemoc Perez-Montiel, Francisco Javier Lopez-Munoz, Carlos Alberto Mendez-Cuesta","doi":"10.2174/0115734064321632241022082028","DOIUrl":"https://doi.org/10.2174/0115734064321632241022082028","url":null,"abstract":"<p><strong>Introduction: </strong>Cervical cancer is a global health problem due to its high incidence and prevalence in women, mainly in third-world countries. For the treatment of this disease, there are different therapeutic options, but these are not always effective, which gives rise to the search for new compounds using cheminformatics tools.</p><p><strong>Objective: </strong>The objective of this study was to design, synthesize, and biologically evaluate N-(2- morpholinoethyl)-2-(naphthalen-2-yloxy)acetamide hydrochloride (1) and 2-(naphthalen-2-yloxy)- N-(2-(piperidin-1-yl)ethyl)acetamide hydrochloride (2) on the HeLa cell line <i>in vitro</i>. The referenced cell line from the American Type Culture Collection (ATCC^®CCL-2^™) was used, and the effect on cell viability was determined by MTT metabolic reduction-based assay at 24, 48, and 72 h.</p><p><strong>Methods: </strong>Therapies directed at the σ1 receptor may be a treatment alternative since this receptor modulates the processes of cell proliferation and angiogenesis, producing cytoprotective or cytotoxic actions depending on the ligand with which it is coupled.</p><p><strong>Results: </strong>The analysis showed that compounds 1 and 2 presented activity on HeLa cancer cells and viability at micromolar concentrations (1.923 μmol/mL and 0.374 μmol/mL, respectively). Moreover, the effect was maintained for 72 h.</p><p><strong>Conclusion: </strong>Naphthaleneacetamide derivatives exhibited an inhibitory effect on the HeLa cell line, and the OSIRIS program predicted less toxicity than cisplatin.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 3","pages":"239-249"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Phytochemicals as Potential Inhibitors of Cancer Cell Metabolic Pathways: A Computational Study.","authors":"Yagyesh Kapoor, Yasha Hasija","doi":"10.2174/0115734064325567240930044647","DOIUrl":"https://doi.org/10.2174/0115734064325567240930044647","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study is to explore the therapeutic potential of phytochemicals in cancer cell metabolism by investigating their ability to inhibit key molecular targets involved in tumor growth and drug resistance.</p><p><strong>Methods: </strong>We evaluated specific phytochemicals against critical cancer-related targets such as GLS1, CKα, MGLL, IDH1, PDHK1, and PHGDH. Molecular docking methods were used to understand the binding interactions between phytochemicals and their selected targets. ADME (absorption, distribution, metabolism, and excretion) analysis and molecular dynamics (MD) simulations were conducted to assess pharmacokinetic properties and ligand-protein interaction dynamics, respectively. MM-PBSA (molecular mechanics Poisson-Boltzmann surface area) calculations were utilized to estimate binding free energies.</p><p><strong>Results: </strong>Molecular dynamics simulations demonstrate that phytochemicals like EGCG, Diosgenin, Withaferin A, and Celastrol exhibit stable binding to their respective targets, suggesting potential therapeutic benefits. Specifically, EGCG shows strong and non-toxic binding affinity with GLS1, making it a promising candidate for cancer treatment.</p><p><strong>Conclusion: </strong>Our study underscores the potential of phytochemicals as effective inhibitors of cancer cell metabolism. The stable binding interactions highlight promising avenues for developing innovative cancer therapies. Further experimental investigations are warranted to validate these findings and advance the development of hybrid phytochemical-based treatments for combating chemoresistance.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 3","pages":"211-228"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of Iodine-Amine Oxidation Approach in the Synthesis of Various N-Alkyl Phosphoramidate Oligonucleotide Derivatives.","authors":"Mikhail D Nekrasov, Dmitrii V Pyshnyi, Maxim S Kupryushkin","doi":"10.2174/0115734064325532241002105426","DOIUrl":"https://doi.org/10.2174/0115734064325532241002105426","url":null,"abstract":"<p><strong>Introduction: </strong>Nowadays, use of phosphate modifications in oligonucleotide backbone has become a common approach for imbuing its structure with the desired beneficial properties. The recent advances in successful application of different classes of phosphate modifications in the design of therapeutic oligonucleotides have led to a renewed interest in the development of approaches for introducing diverse classes of phosphate modifications.</p><p><strong>Methods: </strong>This study aims to investigate the efficiency and optimize protocols for the application of the iodine-amine oxidation reaction to produce various N-alkyl phosphoramidate oligonucleotide derivatives during the conventional solid-phase phosphoramidite synthesis method.</p><p><strong>Results: </strong>Various solvents and drying reagents were tested, and it was evaluated that even minor traces of water in a reaction mixture had a significant impact on yield. Using set of commercially available amines, it was shown that steric accessibility is a more critical parameter than nucleophilicity of the amino group in oxidative amination reaction. It was demonstrated that through use of amino alcohols and diamines during iodine-amine oxidation step various branched oligonucleotide structures can be synthesized.</p><p><strong>Conclusion: </strong>The obtained data indicates that the oxidative amination approach can be a promising tool for preparing various oligonucleotide derivatives during solid-phase synthesis without the use of specialized phosphoramidite monomers.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 3","pages":"229-238"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and Synthesis of 3-(Phenylsulfonamido)benzamide Derivatives as Potent Carbonic Anhydrase IX Inhibitors: Biological Evaluations and Molecular Modeling Studies.","authors":"Mohammad A Khanfar, Mohammad Saleh","doi":"10.2174/0115734064325144240823073504","DOIUrl":"https://doi.org/10.2174/0115734064325144240823073504","url":null,"abstract":"<p><strong>Introduction: </strong>Carbonic anhydrase IX (CAIX) is known to be overexpressed in various tumors and plays a significant role in tumor development and progression.</p><p><strong>Methods: </strong>A series of 3-(benzylsulfonamido)benzamides derivatives was synthesized and tested for their CAIX inhibitory activities. The two most active compounds were subjected to cytotoxicity testing against a panel of 60 cancer cell lines.</p><p><strong>Results: </strong>Many of the synthesized compounds successfully inhibited CAIX activities, exhibiting IC₅₀ values in the low nanomolar range. The most potent CAIX inhibitor was compound 14, with an IC₅₀ of 140 nM. Structure-activity relationship analysis of the synthesized compounds supported with molecular docking revealed strong coordination of sulfonamide moiety with the catalytic Zn²⁺ metal, hydrophobic interactions of the benzylsulfonamido ring with a hydrophobic pocket, and π- stacking interactions of the aryl ring with an aromatic surface. The two most active analogues (10 and 14) were further tested for their antiproliferative activities in the NCI-60 human tumor cell lines. Notably, compound 14 demonstrated potent growth inhibitory effects against several cancer cell lines.</p><p><strong>Conclusion: </strong>The synthesized analogues represent a novel scaffold for the treatment of different types of cancer by targeting CAIX.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 2","pages":"160-167"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Computational Approach Using α-Carbonic Anhydrase to Find Anti-<i>Trypanosoma cruzi</i> Agents.","authors":"Eyra Ortiz-Perez, Domingo Mendez-Alvarez, Alfredo Juarez-Saldivar, Adriana Moreno-Rodríguez, Mariana de Alba Alvarado, Alonzo Gonzalez-Gonzalez, Karina Vazquez, Ana Veronica Martinez-Vazquez, Benjamin Nogueda-Torres, Edgar E Lara-Ramírez, Alma D Paz-Gonzalez, Gildardo Rivera","doi":"10.2174/0115734064310458240719071823","DOIUrl":"10.2174/0115734064310458240719071823","url":null,"abstract":"<p><strong>Background: </strong>Chagas disease has an ineffective drug treatment despite efforts made over the last four decades. The carbonic anhydrase of <i>Trypanosoma cruzi</i> (α-<i>Tc</i>CA) has emerged as an interesting target for the design of new antiparasitic compounds due to its crucial role in parasite processes.</p><p><strong>Objective: </strong>The aim in this study was identify potential α-<i>Tc</i>CA inhibitors with trypanocidal activity.</p><p><strong>Methods: </strong>A maximum common substructure (MCS) and molecular docking were used to carried out a ligand- and structure-based virtual screening of ZINC20 and MolPort databases. The compounds selected were evaluated in an <i>in vitro</i> model against the NINOA strain of <i>Trypanosoma cruzi</i>, and cytotoxicity was determined in a murine model of macrophage cells J774.2.</p><p><strong>Results: </strong>Five sulfonamide derivatives (C7, C9, C14, C19, and C21) had the highest docking scores (-6.94 to -8.31 kcal/mol). They showed key residue interactions on the active site of the α-<i>Tc</i>CA and good biopharmaceutical and pharmacokinetic properties. C7, C9, and C21 had half-maximal inhibitory concentration (IC₅₀) values of 26, 61.6, and 49 μM, respectively, against NINOA strain epimastigotes of <i>Trypanosoma cruzi</i>.</p><p><strong>Conclusion: </strong>Compounds C7, C9, and C21 showed trypanocidal activity; therefore, these results encourage the development of new trypanocidal agents based in their scaffold.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"46-60"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Quinoline Derivatives: Their Antimalarial Efficacy and Structural Features.","authors":"Raghav Mishra, Jayze da Cunha Xavier, Nitin Kumar, Gaurav Krishna, Prashant Kumar Dhakad, Helcio Silva Dos Santos, Paulo Nogueira Bandeira, Tigressa Helena Soares Rodrigues, Diego Romao Gondim, Walber Henrique Ferreira Ribeiro, Draulio Sales da Silva, Alexandre Magno Rodrigues Teixeira, Wandresa Francelino Pereira, Emmanuel Silva Marinho, Sucheta","doi":"10.2174/0115734064318361240827072124","DOIUrl":"https://doi.org/10.2174/0115734064318361240827072124","url":null,"abstract":"<p><strong>Objectives: </strong>Malaria continues to be the primary cause of mortality worldwide, and timely recognition and prompt intervention are crucial in mitigating adverse consequences. This review article aims to examine the effectiveness and structural characteristics of quinoline-based compounds as antimalarial agents. It specifically focuses on their therapeutic effects as well as potential prospects for exploring structure-activity relationship (SAR). In addition, this study aims to identify lead compounds that can efficiently battle multidrug-resistant forms of <i>Plasmodium falciparum </i> and <i>Plasmodium vivax</i>.</p><p><strong>Methods: </strong>A comprehensive review was conducted to evaluate the effectiveness of quinoline-based antimalarial medications in eradicating <i>P. falciparum</i> and <i>P. vivax</i>. The mechanism of action and SAR of these compounds were analyzed.</p><p><strong>Results: </strong>Quinoline-based antimalarials demonstrated significant effectiveness in eliminating <i>P. falciparum</i> parasites, particularly in regions severely impacted by malaria, including Africa and Asia. These compounds were found to exhibit tolerance and immune-modulating properties, indicating their potential for more widespread utilization. The investigation identified various new quinoline compounds with improved antimalarial activity, including metal-chloroquine complexes, diaminealkyne chloroquines, and cinnamoylated chloroquine hybrids. This study explored different mechanisms by which these compounds interact with parasites, including their ability to accumulate in the parasite's acidic food vacuoles and disrupt heme detoxification. The derivatives demonstrated strong efficacy against chloroquine-resistant strains and yielded positive results.</p><p><strong>Conclusion: </strong>Quinoline-based compounds represent a promising avenue for combating malaria due to their demonstrated efficacy against <i>P. falciparum</i> and <i>P. vivax</i> parasites. Further research on their mechanisms of action and SAR could lead to the development of more effective antimalarial medications.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 2","pages":"96-121"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benzimidazole Conjugates as Multi-target Anticancer Agents - A Comprehensive Review.","authors":"R S Remya, N Ramalakshmi, M G Safiya Aaliya, W Blossom Concilia, S Fameetha Thasneem, S Rohini, N Narmadha","doi":"10.2174/0115734064313626240912063644","DOIUrl":"https://doi.org/10.2174/0115734064313626240912063644","url":null,"abstract":"<p><p>Cancer is the second leading cause of mortality globally and is characterized by a multifactorial etiology. Drug resistance and multidrug resistance are the reasons for the failure of many anticancer drugs that are in clinical practice now. The current review is a complete review of benzimidazole hybrids with different heterocyclic rings, which are potential anticancer agents. We reviewed around 70 research works of benzimidazole hybrids published in high-impact journals, along with a short discussion of structural features responsible for its activity against various cancers. This review highlighted benzimidazole hybrids as targeted anticancer agents with effects on multiple targets. Researchers working on targeted medications for cancer treatment will benefit from this review when designing new scaffolds with benzimidazole moieties.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 3","pages":"169-194"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In vitro</i> and <i>In vivo</i> Activity of a New N-Oxide Derivative for Acne Vulgaris Treatment.","authors":"Ivone Leila Lima Delgado, Caue Benito Scarim, Felipe Hugo Alencar Fernandes, Karina Pereira Barbieri, Marisa Campos Polesi, Aline Renata Pavan, Diego Eidy Chiba, Herida Regina Nunes Salgado, Iracilda Zeppone Carlos, Marcos Antonio Correa, Cleverton Roberto de Andrade, Jean Leandro Dos Santos","doi":"10.2174/0115734064306187240722070225","DOIUrl":"10.2174/0115734064306187240722070225","url":null,"abstract":"<p><strong>Introduction: </strong>Furoxan and benzofuroxan are compounds containing an <i>N</i>-oxide function, known for their diverse pharmacological properties, including antimicrobial and antiinflammatory effects. This study aimed to investigate these activities using an in-house library of N-oxide compounds.</p><p><strong>Method: </strong>Twenty compounds were tested against both Gram-positive and Gram-negative bacteria, including <i>Cutibacterium acnes (C. acnes)</i>, a microorganism implicated in the development of acne vulgaris. One compound, (E)-4-(3-((2-(3-hydroxybenzoyl)hydrazone)methyl)phenoxy)-3- (phenylsulfonyl)-1,2,5-oxadiazol-2-N-oxide (compound 15), exhibited selective antimicrobial activity against <i>C. acnes</i>, with a Minimum Inhibitory Concentration (MIC) value of 2 μg/mL. Indirect measurement of Nitric Oxide (NO) release showed that compound 15 and isosorbide dinitrate, when treated with <i>L-cysteine</i>, produced nitrite levels of 20.1% and 9.95%, respectively. Using a NO scavenger (PTIO) in combination with compound 15 in a culture of <i>C. acnes</i> resulted in reduced antimicrobial activity, indicating that NO release is part of its mechanism of action. Cytotoxicity assessments using murine macrophages showed cellular viability above 70% at concentrations up to 0.78 μg/mL.</p><p><strong>Results: </strong>Measurements of Interleukin-1 beta (IL1-β) and Tumor Necrosis Factor-alpha (TNF-α) indicated that compound 15 did not reduce the levels of these pro-inflammatory cytokines. Sustained NO production by inducible Nitric Oxide Synthase (iNOS) in macrophages or neutrophils has been found to be involved in the inflammatory process in acne vulgaris and lead to toxicity in surrounding tissues. Nitrite levels in the supernatant of murine macrophages were found to be decreased at a concentration of 0.78 μg/mL of compound 15, indicating an anti-inflammatory effect. <i>In vivo</i> studies were conducted using Balb/c nude mice inoculated subcutaneously with <i>C. acnes.</i> Cream and gel formulations of compound 15 were applied to treat the animals, along with commercially available anti-acne drugs, for 14 days. Animals treated with a cream base containing 5% of compound 15 exhibited less acanthosis with mild inflammatory infiltration compared to other groups, highlighting its anti-inflammatory properties.</p><p><strong>Conclusion: </strong>Similar results were observed in the benzoyl peroxide group, demonstrating that compound 15 presented comparable anti-inflammatory activity to the FDA-approved drug. These promising results suggest that compound 15 has a dual mechanism of action, with selective antimicrobial activity against <i>C. acnes</i> and notable anti-inflammatory properties, making it a potential prototype for developing new treatments for acne vulgaris.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"32-45"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Role of Natural Topoisomerase Inhibitors as Anticancer agents.","authors":"Sanjeev Kumar Sahu, Manish Vyas, Pranav Kumar Prabhakar","doi":"10.2174/0115734064311729240911102646","DOIUrl":"https://doi.org/10.2174/0115734064311729240911102646","url":null,"abstract":"<p><p>Topoisomerases I and II are the functionally two forms of DNA topoisomerase. In anticancer research, novel anticancer chemotherapeutical capable of blocking topoisomerase enzymes have been discovered. Most commonly, topoisomerase causes replication fork arrest and doublestrand breaks, and this is how a clinically successful topoisomerase-targeting anticancer medicines work. Unfortunately, this novel mechanism of action has been linked to the development of secondary malignancies as well as cardiotoxicity. The specific binding locations and mechanisms of topoisomerase poisons have been identified by studying the structures of topoisomerase-drug-DNA ternary complexes. Recent breakthroughs in science have revealed that isoform-specific human topoisomerase II poison could be created as safer anticancer drug molecules. It may also be able to develop catalytic inhibitors of topoisomerases by focusing on their inactive conformations. In addition to this, the discovery of new bacterial topoisomerase inhibitor molecules and regulatory proteins could lead to the discovery of new human topoisomerase inhibitors. As a result, biologists, organic chemists, and medicinal chemists worldwide have been identifying, designing, synthesizing, and testing a variety of novel topoisomerase-targeting bioactive compounds. This review focused on topoisomerase inhibitors, their mechanisms of action, and different types of topoisomerase inhibitors that have been developed during the last ten years.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 3","pages":"195-210"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}