Medicinal Chemistry最新文献

{"title":"<i>In silico</i> Study of Novel Tryptanthrin-Based Topoisomerase Inhibitors.","authors":"Mukesh Kumar Kumawat, Kapil Kumar","doi":"10.2174/0115734064334604241014024205","DOIUrl":"https://doi.org/10.2174/0115734064334604241014024205","url":null,"abstract":"<p><strong>Background: </strong>Over the past ten years, a remarkable number of changes have occurred in the field of cancer drug research. Most anticancer drugs from the first generation work by breaking down DNA, preventing its production, interfering with cell division processes, or attaching to microtubules. The potential use of tryptanthrin as well as its analogues is well documented for anticancer properties.</p><p><strong>Objective: </strong>To design a novel hybrid of tryptanthrin analogs with expected anticancer activity.</p><p><strong>Methods: </strong>By changing the C-6 carbonyl position of the tryptanthrin molecule, a set of 72 derivatives of substituted-6-benzylidine-6H-indolo[2,1-b] quinazoline-12-one was developed. These ligands were screened <i>in silico</i> using Schrodinger Glide extra precision docking against DNA topoisomerase using doxorubicin and teniposide as references to identify their potential anticancer properties. Further, these ligands were subjected to an <i>in silico</i> ADMET study to identify their drug likeliness.</p><p><strong>Results: </strong>Combined results of molecular docking and <i>in silico</i> ADMET study suggest that out of the total 72 ligands, 6 ligands RC 51, RC 29, RC 42, RC 3, RC 54, and RC 63 were showing very better binding affinity than the natural ligand adenylyl-imidodiphosphate and the two standard reference drugs- doxorubicin and teniposide.</p><p><strong>Conclusion: </strong>Our computational approach was successful in identifying ligands that are potentially potent topoisomerase inhibitors. These can be tested further using <i>in vitro</i> and <i>in vivo</i> analysis.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 6","pages":"516-535"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149509","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":"Arylcarboxamide Derivatives as Promising HDAC8 Inhibitors: An Overview in Light of Structure-activity Relationship and Binding Mode of Interaction Analysis.","authors":"Suvankar Banerjee, Sandip Kumar Baidya, Tarun Jha, Balaram Ghosh, Nilanjan Adhikari","doi":"10.2174/0115734064329669241007060848","DOIUrl":"https://doi.org/10.2174/0115734064329669241007060848","url":null,"abstract":"<p><p>HDAC8 is associated with several disease conditions as well as various cancers of several organs and hematological malignancies. To counter such pathophysiological and disease conditions, inhibition of HDAC8 may be a promising approach for anticancer drug development. In this article, a detail of arylcarboxamide-based potential HDAC8 inhibitors has been outlined. Considering their binding pattern of interactions along with the chemical features, effective and selective novel HDAC8 inhibitors can be designed further. Therefore, modification of these compounds provides greater possibilities for the development of novel HDAC8 inhibitors. Nevertheless, structural modification of such arylcarboxamide derivatives may be able to produce potent dual-inhibitory compounds along with HDAC8 inhibition. Thus, this article is quite useful for exploring and identifying several possibilities for arylcarboxamide-based HDAC8 inhibitors. Moreover, it can be concluded that further study of the arylcarboxamide-based HDAC8 inhibitors can be effectively used for the treatment of different cancerous and non-cancerous diseases.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 6","pages":"471-500"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149517","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":"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":"Promising Anticancer Activity of Pyrazole Compounds against Glioblastoma Multiforme: Their Synthesis, <i>In vitro</i>, and Molecular Docking Studies.","authors":"Kemal Alp Nalcı, Cihat Mete, Zeynep Demir, İshak Bildirici, Adnan Cetin","doi":"10.2174/0115734064337582241103172720","DOIUrl":"10.2174/0115734064337582241103172720","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma Multiforme (GBM), a highly aggressive and prevalent brain cancer with a higher incidence in males, has limited treatment success due to drug resistance, inadequate targeting and penetration of cancer cells, and an incomplete understanding of its molecular pathways. GBM is a highly aggressive brain cancer with limited treatment options. This study investigates the anticancer potential of synthesized pyrazole compounds against GBM cells.</p><p><strong>Methods: </strong>A series of pyrazole derivatives were synthesized and tested for their efficacy against GBM using MTT assays. Molecular docking studies were conducted to explore the binding interactions of these compounds with GBM receptors.</p><p><strong>Results: </strong>Compounds 3 and 5 demonstrated significant anticancer activity, reducing cell viability more effectively than the control group. MTT assay results confirmed their potency. Molecular docking studies revealed strong binding interactions with GBM receptors, highlighting their potential as anticancer agents.</p><p><strong>Conclusion: </strong>The study evaluated the anticancer activity of synthesized compounds on human GBM cells, with compounds 3 and 5 showing the most promising results. Pyrazole 3 significantly reduced cell viability at high concentrations, while both pyrazoles 3 and 5 required higher doses to achieve substantial effects, as indicated by their IC₅₀ values. Molecular docking studies confirmed strong binding interactions with the GBM receptor, and the pharmacokinetic properties suggest their potential as anticancer agents. These results highlight compounds 3 and 5 as candidates for further investigation.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"536-545"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007875","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 silico</i> Identification and Computational Screening of Potential AFP Inhibitors Against Liver Cancer.","authors":"Hassan Bin Waseem, Muhammad Shakeel, Faiz-Ul Hassan, Asma Yaqoob, Azhar Iqbal, Amna Khalid, Hafiza Nisha Akram, Noshaba Dilbar, Saad Qamar, Rana Adnan Tahir, Sheikh Arslan Sehgal","doi":"10.2174/0115734064330103250106034126","DOIUrl":"10.2174/0115734064330103250106034126","url":null,"abstract":"<p><strong>Introduction: </strong>Liver cancer is considered one of the most common types of cancer and a major cause of ephemerality worldwide having a higher prevalence rate in Asia and sub-Saharan Africa. The alpha-fetoprotein (AFP) is a serum glycoprotein that belongs to a class of oncodevelopmental proteins and is also involved in tumor formation.</p><p><strong>Methods: </strong>In the current effort, a hybrid approach of virtual screening followed by pharmacophore generation and molecular dynamic simulation analyses were performed. The screened top-ranked 10 docked compounds from the selected anti-cancer compound library were utilized to generate the ligand-based pharmacophore. Virtual screening was performed two-dimensional similarity search against the selected natural compound library based on their physicochemical properties. It was observed that all the compounds from the anti-cancer compound library and natural compound library showed similar binding resides.</p><p><strong>Results: </strong>Therefore, the top-ranked screened compounds that showed the least binding energy and highest binding affinity against AFP, obtained through the anti-cancer drug library and natural compound library were reported. The molecular docking analyses revealed that Leu-219, His-222, Lys-242, Lys-246, His-316, Glu-318, Ala-366, Val-367, Gly-475, Ile-479, Ala-471, Asp-478 were observed as potential residues for interaction.</p><p><strong>Conclusion: </strong>The observed results of virtual screening, molecular docking, and MD simulation analyses entail noteworthy observations illustrating that NC002 was a potent inhibitor. The proposed compound NC002 may have potential against liver cancer by targeting AFP based on MD simulation analyses, PCA, and MM-GBSA.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"554-565"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414644","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":"Design and Synthesis of (2,3-dichloro-4-(3-(substituted Phenyl)acryloyl) phenoxy) Substituted Carboxylic Acid as Potent Glutathione-s-transferase Inhibitors, Anti-breast-cancer Agents and Enhancing Therapeutic Efficacy of Anticancer Agents.","authors":"Afreen Begum Abdul Qayyum, Syed Ayaz Ali, Santosh Namdeo Mokale","doi":"10.2174/0115734064316508240911032442","DOIUrl":"https://doi.org/10.2174/0115734064316508240911032442","url":null,"abstract":"<p><strong>Background: </strong>Ethacrynic acid is a dynamic agent holding alpha-beta unsaturated carbonyl unit in its structure which imparts superiority and extraordinary advantage of displaying multiple biological activities such as anticancer, antiviral, anti-malarial effect, diuretic effect and inhibits the Glutathione-s-transferase p1-1 enzyme which produces hindrance in the pathway of apoptosis. Ethacrynic acid is an inhibitor of Glutathione-s-transferases. EtA by itself act as an anticancer agent at higher concentration and also increases effectiveness of other compounds used in cancer treatment by preventing their detoxification, all these facts attracted our attention to develop and evaluate novel structural analogues of ethacrynic acid for their inhibitory effect on GSTs and anti-cancer activity in breast cancer.</p><p><strong>Objective: </strong>By attending rational drug design perspectives the research is aimed to develop and evaluate novel structural analogues of ethacrynic acid as Inhibitors of GSTs enzyme and with antibreast cancer activity.</p><p><strong>Methods: </strong>Designed compounds were synthesized as per convenient route shown in the scheme of synthesis. Molecular docking studies were done against GSTP1-1 (PDB:3HJO). Structures of novel synthesized molecules were confirmed by spectral characterization such as FTIR, ¹HNMR, ¹³CNMR and Mass spectrometry. ADME studies were done to ensure safety and drug like properties of the compounds. Ten structural analogues of ethacrynic acid were synthesized and evaluated for their inhibitory effect on activity of Glutathione-s-transferases which was measured by performing assay method. <i>In-vitro</i> anti-breast cancer activity was done on MCF-7 and MDAMB-231 cell line by MTT assay.</p><p><strong>Results: </strong>Compound A3, A5 and A6 were found with greater inhibition of the activity of GSTs and maximum anti-proliferative activity in breast cancer.</p><p><strong>Conclusion: </strong>We have effectively developed novel compounds possessing structural resemblance with ethacrynic acid Compounds of the series has shown moderate to higher inhibitory effect on GSTs and anti-proliferative activity in breast cancer. The compound A3 was found to be promising agent with high level of potency in each biological response. The research studies presented here may be an enlightening path in development of novel therapeutic agents with high level of inhibition in the activity of GSTs and anti-breast cancer effect.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 4","pages":"319-330"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003371","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 Silico</i> Discovery and Predictive Modeling of Novel Acetylcholinesterase (AChE) Inhibitors for Alzheimer's Treatment.","authors":"Humaera Noor Suha, Md Shamim Hossain, Shofiur Rahman, Abdullah N Alodhayb, Md Mainul Hossain, Sarkar M A Kawsar, Raymond A Poirier, Kabir M Uddin","doi":"10.2174/0115734064304100240511112619","DOIUrl":"10.2174/0115734064304100240511112619","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease, akin to coronary artery disease of the heart, is a progressive brain disorder driven by nerve cell damage.</p><p><strong>Methods: </strong>This study utilized computational methods to explore 14 anti-acetylcholinesterase (AChE) derivatives (1 ̶ 14) as potential treatments. By scrutinizing their interactions with 11 essential target proteins (AChE, Aβ, BChE, GSK-3β, MAO B, PDE-9, Prion, PSEN-1, sEH, Tau, and TDP-43) and comparing them with established drugs such as donepezil, galantamine, memantine, and rivastigmine, ligand 14 emerged as notable. During molecular dynamics simulations, the protein boasting the strongest bond with the critical 1QTI protein and exceeding drug-likeness criteria also exhibited remarkable stability within the enzyme's pocket across diverse temperatures (300- 320 K). In addition, we utilized density functional theory (DFT) to compute dipole moments and molecular orbital properties, including assessing the thermodynamic stability of AChE derivatives.</p><p><strong>Result: </strong>This finding suggests a well-defined, potentially therapeutic interaction further supported by theoretical and future <i>in vitro</i> and <i>in vivo</i> investigations.</p><p><strong>Conclusion: </strong>Ligand 14 thus emerges as a promising candidate in the fight against Alzheimer's disease.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"345-366"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158633","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":"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}

{"title":"Pharmacological Evaluation of Bioisosterically Replaced and Triazole- Tethered Derivatives for Anticancer Therapy.","authors":"Dipesh Kumar, Salahuddin, Avijit Mazumder, Rajnish Kumar, Mohamed Jawed Ahsan, Mohammad Shahar Yar, Abbussalam, Pankaj Kumar Tyagi, M V N L Chaitanya","doi":"10.2174/0115734064320533240903062533","DOIUrl":"https://doi.org/10.2174/0115734064320533240903062533","url":null,"abstract":"<p><p>Cancer has been the cause of the highest number of deaths in the human population despite the development and advancement in treatment therapies. The toxicity, drug resistance, and side effects of the current medicaments and therapies have left the void for more research and development. One of the possibilities to fill this void is by incorporating Triazole moieties within existing anticancer pharmacophores to develop new hybrid drugs with less toxicity and more potency. The placement of nitrogen in the triazole ring has endowed its characterization of being integrated with anticancer pharmacophores via bioisosteric replacement, click chemistry and organocatalyzed approaches. This review paper emphasizes the discussions from articles published from the early 2000s to the current 2020s about the triazole-based derivatives used in anticancer therapy, elaborating more on their chemical structures, target receptors or enzymes, mechanism of action, structure-activity relationships, different triazole-derived hybrid drugs under clinical and nonclinical trials, and recent advancements toward developing more potent and less toxic anticancer agents.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 4","pages":"264-293"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989702","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}