Medicinal Chemistry最新文献

{"title":"Recent Developments in Azetidinone-Azole Conjugates: Emerging Antimicrobial Potentials.","authors":"Dinesh Kumar Mehta, Rajiv Chaurasiya, Rina Das","doi":"10.2174/0115734064355361241230063744","DOIUrl":"https://doi.org/10.2174/0115734064355361241230063744","url":null,"abstract":"<p><p>The emergence of multidrug-resistant microbial strains poses a significant challenge to global public health. In response, researchers have been exploring innovative antimicrobial agents with enhanced efficacy and novel mechanisms of action. One promising approach involves the synthesis of hybrid molecules combining azetidinone and azole moieties, capitalizing on the respective antimicrobial properties of both structural elements. Natural and synthetic azetidinone derivatives hold a prominent position among medicinally significant compounds due to their varied and potent antibiotic activities. Interest persists in discovering new synthetic methods and refining existing ones, as well as applying these methods to create novel, biologically active azetidinone derivatives. Additionally, azoles are highly regarded in pharmaceuticals for their broad efficacy, tolerability, and oral availability. By merging these two pharmacophores, researchers aim to create compounds with synergistic or additive antimicrobial effects, potentially overcoming existing resistance mechanisms. Various synthetic strategies, including click chemistry and multicomponent reactions, have been employed to prepare these hybrid molecules efficiently. The antimicrobial potential of azetidinone-azole conjugates has been extensively evaluated against a spectrum of pathogens, including bacteria, fungi, and protozoa. These studies have demonstrated promising results, with several compounds exhibiting potent activity against both Gram-positive and Gramnegative bacteria, as well as clinically relevant fungal strains. Furthermore, SAR studies have provided valuable insights into the key structural features governing the antimicrobial properties of these conjugates, facilitating further optimization and rational design. In conclusion, the development of azetidinone-azole hybrids represents a promising avenue in the quest for novel antimicrobial agents. This study presents a comprehensive overview of recent advancements in synthesis and antimicrobial evaluation of azetidinone-azole conjugates.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951264","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":"Marine-Derived Compound Targeting mTOR and FGFR-2: A Promising Strategy for Breast, Lung, and Colorectal Cancer Therapy.","authors":"Vijay Murali Ravi Mythili, Kumaran K, Sayantani Chattopadhyay, Shahjahan Ahmad Basha, Sruthi Sekar, Sowmya Senthil, Prabhu D, Kirubakaran Rangasamy, K N ArulJothi","doi":"10.2174/0115734064346419241104110015","DOIUrl":"https://doi.org/10.2174/0115734064346419241104110015","url":null,"abstract":"<p><strong>Introduction: </strong>The marine habitat is a plentiful source of diverse, active compounds that are extensively utilised for their medicinal properties. Pharmaceutical trends have currently changed towards utilising a diverse range of goods derived from the marine environment.</p><p><strong>Method: </strong>This study aimed to examine the inhibitory effects of bioactive chemicals derived from marine algae and bacteria. The identification of these compounds was carried out through the process of Gas Chromatography-Mass Spectrometry (GC-MS) profiling. Subsequently, these compounds were subjected to docking simulations against a specific set of target proteins that are known to be frequently overexpressed in three distinct types of cancer.</p><p><strong>Result: </strong>From the docking results, the ligand 1,4:3,6:5,7-Tribenzal-beta-mannoheptitol was found to be effective against the proteins mTOR (PDB ID: 4JSV) and FGFR2 (PDB ID:6V6Q). The findings of this study highlight the significant benefits offered by the tool under investigation, which effectively enhances the efficiency of the docking procedures.</p><p><strong>Conclusion: </strong>These compounds hold significant potential for further development and exploration in the field of cancer therapeutics.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951262","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":"Extraction, Isolation and Purification of Catechins and their Applications.","authors":"Hong-Mei Cao, Jiao-Jiao Fang, Yi-Tao Zhao, Pei-Hong Zhao, Xin Chen","doi":"10.2174/0115734064353669241212064640","DOIUrl":"https://doi.org/10.2174/0115734064353669241212064640","url":null,"abstract":"<p><p>Catechins, the main active components of tea polyphenols, boast remarkable antioxidant activities because of their unique structures. This translates to a range of potential health benefits, including fighting antibacterial, inflammation, and even cancers. However, extracting these beneficial compounds can be tricky as they're prone to degradation. Thankfully, recent advancements have yielded successful methods for isolating and purifying catechins, allowing us to obtain them in their purest form. The power of catechins isn't just theoretical. In vitro and in vivo studies have demonstrated promising results in treating various conditions like inflammation, cancer, neurodegenerative diseases, cardiovascular diseases, diabetes, and more. This review dives deep into the methods used to extract, isolate, and purify catechins. Additionally, it explores their potent antioxidant activities and exciting possibilities for future applications.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951317","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":"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":"Synthesis, Antimicrobial Activity, DFT, Molecular Docking, and Dynamic Simulations of Trityl Mannopyranoside Derivatives for Potential Antibacterial Agents.","authors":"Sabina Akter, Sarkar M A Kawsar, Gassoumi Bouzid, Mabrouk Horchani, Md Z H Bulbul, Houcine Ghalla, Hichem Ben Jannet, Supriyo Saha, Yuki Fujii, Kabir M Uddin, Ajmal R Bhat, Sumeer Ahmed, Yasuhiro Ozeki","doi":"10.2174/0115734064339243241027024304","DOIUrl":"10.2174/0115734064339243241027024304","url":null,"abstract":"<p><strong>Aim: </strong>There is an urgent need for new antimicrobial compounds with alternative modes of action for the treatment of drug-resistant bacterial and fungal pathogens.</p><p><strong>Background: </strong>Carbohydrates and their derivatives are essential for biochemical and medicinal research because of their efficacy in the synthesis of biologically active drugs.</p><p><strong>Objective: </strong>In the present study, a series of methyl α-D-mannopyranoside (MMP) derivatives (2-6) were prepared via direct acylation, and their biological properties were characterized.</p><p><strong>Methods: </strong>The structures of synthesized compounds were established by analyzing their physicochemical, elemental, and spectroscopic data and evaluating their in vitro antimicrobial activities through <i>in silico</i> studies.</p><p><strong>Results: </strong>In the antibacterial study, compound 3 was found to be mostly active toward most of the organisms, exhibiting maximum inhibition of <i>S. abony</i> and minimum inhibition of <i>P. aeruginosa</i>. However, the MIC and MBC values revealed that this compound is highly effective against <i>Bacillus subtilis</i> (MIC of 0.5 μg/L and MBC of 256 μg/L). In terms of antifungal activity, 3 and 6 showed the most promising activity toward <i>Aspergillus flavus</i>, with an inhibition of 95.90 ± 1.0% for compound 3 and 96.72 ± 1.1% for compound 6. Moreover, density functional theory (DFT) in conjunction with the BLYP/6-311G (d) basis sets was used to calculate the dipole moment and total energy for each compound, and the molecular electrostatic potential and Mulliken charge were considered to study the electrophilicity and nucleophilicity of the groups in each compound. For dipole moment calculations, the dipole moments are in the following order: 6 < 3 < 1 < 5 < 2 < 4, inferring that compounds 2 and 4 possess a high dipole moment in comparison with the other inhibitor systems. Furthermore, molecular docking was performed against threonine synthase from <i>B. subtilis</i> ATCC 6633 (PDB: 6CGQ) to identify the active site of the compounds, with compound 3 showing a maximum binding energy of -10.3 kcal/mol and compound 4 exhibiting a binding energy of -10.2 kcal/mol. In addition, a 100 ns MD simulation was performed, and the results revealed a stable conformation and binding pattern within the stimulating environment.</p><p><strong>Conclusion: </strong>Our synthetic, antimicrobial, and in silico experiments revealed that MMP derivatives exhibit potential activity, providing a therapeutic target for bacteria and fungi.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"403-424"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932327","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, Synthesis, Characterization, and Antitumor Activities of Benzimidazole-functionalized Organoruthenium Complexes Bearing Fluorine Group.","authors":"Ramazan Pasahan, Ozlem Demirci, Irmak Icen Taskin, Aziz Pasahan, Meryem Rüveyda Sever, Yetkin Gok, Aydın Aktas","doi":"10.2174/0115734064331622241113032042","DOIUrl":"10.2174/0115734064331622241113032042","url":null,"abstract":"<p><strong>Background: </strong>This work presents the synthesis of Ru(II)NHC complexes bearing a series of 4-fluorobenzyl group. These complexes have been characterized by a variety of spectroscopic methods (¹H NMR, ¹³C NMR, and FTIR) and by elemental analysis techniques.</p><p><strong>Methods: </strong>These complexes' antitumor activities against SH-SY5Y (human neuroblastoma) and <i>HCT116</i> (human colon cancer) were investigated by 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) assay.</p><p><strong>Results: </strong>The results showed that all the synthesized complexes exhibited significant cytotoxic effect with low IC₅₀ values 15 ± 0.57, 15.26 ± 0.71, 7.64 ± 0.30, 27.66 ± 0.36 and 14.45 ± 0.84 (μg/mL) respectively.</p><p><strong>Conclusion: </strong>Furthermore, apoptosis assessed by double labeling with Annexin V-FITC/PI indicated that complexes 1b and 1d can effectively induce apoptosis and inhibit cell proliferation at the S phase in <i>SH-SY5Y</i> cells. Taken together, Ru(II)NHC complexes containing the 4- fluorobenzyl group have significant potential for the development of novel, highly effective anticancer agents.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"546-553"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414702","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":"Integrated Artificial Intelligence and Physics-Based Methods for the <i>De novo</i> Design of Spleen Tyrosine Kinase (SYK) Inhibitors.","authors":"Atul Darasing Pawar, Heba Taha M Abdelghani, Hemchandra Deka, Monishka Srinivas Battula, Surajit Maiti, Pritee Chunarkar Patil, Shovonlal Bhowmick, Rupesh V Chikhale","doi":"10.2174/0115734064333216250110034315","DOIUrl":"10.2174/0115734064333216250110034315","url":null,"abstract":"<p><strong>Introduction: </strong>SYK (Spleen Tyrosine Kinase) regulates immune response and is a promising target for cancer, sepsis, and allergy therapies. This study aims to create novel compounds that serve as alternative inhibitors for cancer treatments targeting SYK.</p><p><strong>Methods: </strong>A thorough combination of machine learning (ML) and physics-based methods was employed to achieve these goals, encompassing <i>de novo</i> design, multitier molecular docking, absolute binding affinity computation, and molecular dynamics (MD) simulation.</p><p><strong>Results: </strong>A total of 5576 novel molecules with key pharmacophoric features were generated using an ML-driven de novo approach against 21 diaminopyrimidine carboxamide analogs. Pharmacokinetic and toxicity evaluation assisted by the ML approach revealed that 4353 chemical entities fulfilled the acceptable pharmacokinetic and toxicity profiles. By screening through binding energy threshold from the physics-based multitier molecular docking, and ML-assisted absolute binding affinity identified the top four molecules such as RI809 (2-([1,1'-biphenyl]-3-ylmethyl)-4-((2- aminocyclohexyl)oxy)benzamide), RI1393 (4-((2-aminocyclohexyl)amino)-2-(3-(1-methyl-1Hpyrazol- 5-yl)-4-(trifluoromethyl)benzyl)benzamide), RI2765 (2-([1,1'-biphenyl]-3-ylmethyl)-4-((4- aminocyclohexyl)methyl)benzamide), and RI3543 (2-([1,1'-biphenyl]-2-ylmethyl)-4-(piperidin-3- yloxy)benzamide). The final molecules identified exhibit a strong affinity for SYK, attributed to their structural diversity and notable pharmacophoric characteristics. All-atom MD simulations showed that each final molecule retained significant binding interactions with SYK and stability in dynamic states, indicating their potential as anticancer agents. Calculated binding free energy for selected molecules using molecular mechanics with generalized Born and surface area (MMGBSA) ranged from -6 to -35 kcal/mol, indicating strong SYK affinity.</p><p><strong>Conclusion: </strong>In conclusion, the integration of AI and physics-based methods successfully developed promising SYK inhibitors with significant potential. The molecules reported could be vital anticancer agents subjected to experimental validation.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"566-581"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720202","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":"Efficient Synthesis of Mannopyranoside-based Fatty Acyl Esters: Effects of Acyl Groups on Antimicrobial Potential.","authors":"Md Lutfor Rahaman, Md Atiqur Rahman, Md Mohin Hasnain, Mohammad Amran, Talha Bin Emran, Md Ashikur Rahaman Khan, Md Abdul Majed Patwary, Mohsin Kazi, Mohammed Mahbubul Matin","doi":"10.2174/0115734064292665240523113515","DOIUrl":"10.2174/0115734064292665240523113515","url":null,"abstract":"<p><strong>Background: </strong>The approval of Sucrose Fatty Acid Esters (SFAEs) as food additives/ preservatives with antimicrobial potential has triggered enormous interest in discovering new biological applications. Accordingly, many researchers reported that SFAEs consist of various sugar moieties, and hydrophobic side chains are highly active against certain fungal species.</p><p><strong>Objective: </strong>This study aimed to conduct aregioselective synthesis of SAFE and check the effect of chain length and site of acylation (i.e., C-6 vs. C-2, C-3, C-4, and long-chain vs. short-chain) on antimicrobial potency.</p><p><strong>Methods: </strong>A direct acylation method maintaining several conditions was used for esterification. <i>In vitro</i> tests, molecular docking, and in silico studies were conducted using standard procedures.</p><p><strong>Results: </strong><i>In vitro</i> tests revealed that the fatty acid chain length in mannopyranoside esters significantly affects the antifungal activity, where C12 chains are more potent against Aspergillus species. In terms of acylation site, mannopyranoside esters with a C8 chain substituted at the C-6 position are more active in antifungal inhibition. Molecular docking also revealed that these mannopyranoside esters had comparatively better stable binding energy and hence better inhibition, with the fungal enzymes lanosterol 14-alpha-demethylase (3LD6), urate oxidase (1R51), and glucoamylase (1KUL) than the standard antifungal drug fluconazole. Additionally, the thermodynamic, orbital, drug-likeness, and safety profiles of these mannopyranoside esters were calculated and discussed, along with the Structure-Activity Relationships (SAR).</p><p><strong>Conclusion: </strong>This study thus highlights the importance of the acylation site and lipid-like fatty acid chain length that govern the antimicrobial activity of mannopyranoside-based SFAE.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"385-402"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262250","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":"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":"Synthesis, Characterization, and <i>In Vitro</i> and <i>In Silico</i> Studies of New Triazole Derivatives as Aromatase Inhibitors.","authors":"Zeynep Livanur Uzmez, Derya Osmaniye, Yusuf Ozkay, Zafer Asım Kaplancıklı","doi":"10.2174/0115734064316112240722092935","DOIUrl":"https://doi.org/10.2174/0115734064316112240722092935","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer is the most common type of cancer among women. Steroidal or non-steroidal aromatase inhibitors (NSAIs) are used clinically, and in most cancer diseases, resistance is the most important problem.</p><p><strong>Methods: </strong>The nitrogenous heterocyclic ring is noteworthy in the structure of non-steroidal aromatase inhibitors. This is the pharmacophore structure for aromatase inhibition. Because the enzyme interacts with the Fe²⁺ cation of the HEM structure in its active site, the most used agents in the clinic, such as anastrozole and letrozole, contain triazoles in their structures. Within the scope of this study, hybrid compounds containing both imidazole and triazole were synthesized.</p><p><strong>Results: </strong>The synthesis was carried out by a 4-step reaction. The anticancer effects of the compounds were evaluated by MTT assay performed on A549 and MCF-7 cancer cells. Compound 4d showed anticancer activity against the MCF-7 cell line with IC₅₀=6.7342 uM value. This compound exhibited anticancer activity against the A549 cell line with an IC₅₀ = 17.1761 μM. In the MTT test performed on a healthy cell line to determine the cytotoxic effects of the compounds, the compound showed activity with a value of 4d IC₅₀=13.2088 uM. This indicates that the compound is not cytotoxic. Additionally, BrdU analysis was performed to evaluate whether the compound inhibits DNA synthesis. These selective effects of the compounds on breast cancer strengthened their aromatase enzyme inhibitor potential. For this reason, experiments conducted with both <i>in vitro</i> and <i>in silico</i> methods revealed a compound with high aromatase inhibitor potential.</p><p><strong>Conclusion: </strong>The interactions observed as a result of molecular docking and dynamics studies are in harmony with activity studies. In particular, interactions with HEM600 demonstrate the activity potential of the compound.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 4","pages":"309-318"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021130","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}