Medicinal Chemistry最新文献

{"title":"Design, Synthesis, and Biological Evaluation of a Novel Series of Thiazolidinediones as Dual GSK-3ß and Tau Aggregation Inhibitors.","authors":"Zahra Abdollahi, Khalil Abnous, Mohamad Reza Kalani, Seyed Mohammad Taghdisi, Somaieh Soltani, Mojgan Nejabat, Farzin Hadizadeh","doi":"10.2174/0115734064369119250413021648","DOIUrl":"https://doi.org/10.2174/0115734064369119250413021648","url":null,"abstract":"<p><strong>Introduction: </strong>Glycogen synthase kinase-3β (GSK-3β) is a serine/threonine kinase that is involved in the synthesis of glycogen. Among the inhibitors, thiazolidinediones (TZDs) can specifically bind to GSK-3ß. They act non-competitively with ATP, and as a result, they are very specific and have fewer side effects. In this research, new TZDs were designed and synthesized, and then their inhibitory effects on GSK-3β enzyme and tau aggregation were investigated.</p><p><strong>Material and methods: </strong>The structure of the compounds was confirmed using 1H-NMR, 13CNMR, and LC-MASS. The inhibitory activities of the compounds 5a-p, against GSK-3ß were evaluated using Z'-LYTE technique, and the IC50 values were determined.</p><p><strong>Results: </strong>Compound 5l (R1 = Me, R2 = 4-F-benzyl, R3 = butyl) with IC50 of 16.1 μM exhibited the most potent inhibition. Also, the binding with tau protein and their inhibitory effects on the accumulation of recombinant human tau protein (1N4R, htau34) were evaluated using the Surface Plasmon Response (SPR) method. In this study also the impact of TZDs on tau aggregation using the Thioflavin T (ThT) assay was investigated. PC12 cells viability study confirmed the neuroprotective effects of compounds against tau aggregates. MD simulation studies showed the interaction of 5l with the active site of GSK-3b (PDB ID: 2OW3) and also its destructive effect on tau aggregate (PDB ID: 5O3L) was studied.</p><p><strong>Conclusion: </strong>Overall, the study identified three promising TZDs with potential as inhibitors of GSK-3β and tau proteins, highlighting compound 5l as particularly effective in stabilizing GSK- 3β and disrupting tau aggregation.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028971","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":"Curcumin-Based Virtual Screening Identifies Inhibitors of SARS-CoV-2 Spike Protein and ACE2 Receptor Binding.","authors":"Timoteo Delgado-Maldonado, Luis D Gonzalez-Morales, Gilberto Vargas-Salas, Guadalupe Rojas-Verde, Eyra Ortíz-Pérez, Alma D Paz-Gonzalez, Gildardo Rivera","doi":"10.2174/0115734064371154250414064157","DOIUrl":"https://doi.org/10.2174/0115734064371154250414064157","url":null,"abstract":"<p><strong>Background: </strong>To date, COVID-19 has caused over 772 million cases, with approximately 7 million deaths, according to the World Health Organization. Therefore, there is a need to develop new drugs to address the challenges posed by this disease.</p><p><strong>Objective: </strong>To propose new antiviral agents based on the natural product curcumin as potential protein-protein interaction inhibitors between the SARS-CoV-2 spike receptor binding domain (RBD) and the ACE2 receptor.</p><p><strong>Methods: </strong>A curcumin-based virtual screening was performed (Tanimoto coefficient= 0.9), and molecular docking analysis were carried out using the RBD as a receptor. Molecular dynamics (MD) using GROMACS were conducted for 120 ns. The SwissADME server was used to predict pharmacokinetics. To validate predictions, an in vitro enzyme assay measuring the relative inhibition of the interaction between the RBD and the ACE2 receptor was performed.</p><p><strong>Results: </strong>More than 1300 ligands were evaluated through molecular docking. The docking results were analyzed, and the ligands were classified according to their score and profile of interactions with residues of the RBD of the SARS-CoV-2 S glycoprotein. The top ten with the best scores and interactions were selected to verify the commercial availability. The lead compound Cu-1 demonstrated significant interactions with the RBD and stability in MD simulations, was acquired and evaluated in vitro. Compound Cu-1 inhibited 36 ± 0.7 % the interaction between the SARSCoV- 2 spike and the ACE2 receptor. In addition, Cu-1 was shown to have an acceptable druglikeness and pharmacokinetic profile.</p><p><strong>Conclusion: </strong>Curcumin provides a scaffold for identifying novel compounds with potential antiviral activity. Further studies on compound Cu-1 could yield on optimizing its structure to increase activity targeting the RBD of the S glycoprotein.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032022","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":"Scaffold Hopping and Optimization of Thiazole Hybrids as Selective PIN1 Inhibitors: A Computational Study.","authors":"Meeramol C Chellappan, Soumya Vasu, Shriraam Mahadevan, M K Kathiravan, J Saravanan, Soniya Naik, Knolin K Thachil","doi":"10.2174/0115734064376657250416071044","DOIUrl":"https://doi.org/10.2174/0115734064376657250416071044","url":null,"abstract":"<p><strong>Background: </strong>Protein Interacting with NIMA1 (PIN1) is a distinct enzyme, known as a peptidyl-prolyl cis-trans isomerase (PPIase), which catalyzes the cis-trans isomerization of amide bonds in proteins containing phosphoserine/threonine-proline (pSer/Thr-Pro) motifs, presenting a unique therapeutic opportunity for addressing multiple disorders.</p><p><strong>Methods: </strong>A series of 140 thiazole compounds were created using the shape similarity technique with the intention of discovering effective PIN1 inhibitors with a new scaffold. The designed compounds were docked into the enzyme's ATP binding site, and the binding free energies for all docked conformations were calculated. The compounds were evaluated for their ADMET and drug-likeness properties. Following the identification of top candidates, molecular dynamics simulations were conducted to investigate the binding dynamics of the highest-scoring compound.</p><p><strong>Results: </strong>Based on computational findings, sixteen compounds were identified as potential PIN1 inhibitors. Among the sixteen compounds, four (S8Ba, S8Bb, S8Bd, and S8Bd) exhibited the most favorable ADMET profiles and robust interactions with key PIN1 residues. Molecular dynamics simulations confirmed that S8Ba and S8Bd exhibited the most promising activity over 100ns.</p><p><strong>Conclusion: </strong>The results corroborated the docking outcomes, validating the selected hits as potential PIN1 inhibitors. This breakthrough could influence the development of therapeutic leads for combating diabetes, cancer, and Alzheimer's disease.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989635","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":"Reducing Cabozantinib Toxicity in Renal Cell Carcinoma Treatment through Structural Modifications.","authors":"Jiaxiang Guo, Xiaotao Yin, Yongliang Lu, Yu Yang","doi":"10.2174/0115734064374511250411104320","DOIUrl":"https://doi.org/10.2174/0115734064374511250411104320","url":null,"abstract":"<p><strong>Background and objectives: </strong>Cabozantinib, a Tyrosine Kinase Inhibitor (TKI), is widely used in Renal Cell Carcinoma (RCC) therapy but often causes serious side effects such as myelosuppression, immunosuppression, and angiopathy. This study aims to identify key protein targets responsible for the therapeutic efficacy and adverse reactions of cabozantinib and to explore structural modifications to reduce toxicity while preserving efficacy.</p><p><strong>Methods: </strong>A non-randomized computational approach was employed, screening 400 potential protein targets using SwissTargetPrediction and ChemBL databases. Molecular docking and Structure-Activity Relationship (SAR) analysis were performed to assess interactions between cabozantinib and identified targets, focusing on structural elements contributing to toxicity.</p><p><strong>Results: </strong>Three primary proteins were identified as responsible for the anti-tumor effects of cabozantinib, while three others were linked to its side effects. Docking analysis revealed that the methoxyphenyl group in cabozantinib formed undesirable hydrogen bonds with toxicity-related proteins. Modulating these off-target interactions by minimizing hydrogen bonding in this region could significantly reduce adverse effects.</p><p><strong>Conclusion: </strong>These findings provide structural insights into cabozantinib's dual effects and suggest optimization strategies for TKI design, offering a pathway toward safer and more effective RCC treatments.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032219","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":"Pyrazole and Pyrazoline-Based EGFR TK Inhibitors: A Review Study Emphasizing Structure-Activity Relationship (SAR).","authors":"Shruti Mittal, Ozair Alam, Lakshay Singh, Kannan, Aasma Shakuli, Vishal Mathur, Mukund Jha, Anam Ilyas, Shaheen Ali, Mohd Javed Naim, Sana Tanweer","doi":"10.2174/0115734064373755250409165138","DOIUrl":"https://doi.org/10.2174/0115734064373755250409165138","url":null,"abstract":"<p><p>Unusual cell growth patterns, metastasis (the spread of tumors to other parts of the body), and potential death are all hallmarks of cancerResearch in oncology clearly shows that abnormalities in EGFR expression directly contribute to uncontrolled cell growth and division, resulting in the development of carcinomas.. People with cancer have developed resistance due to mutations in several EGFR-associated genes. Tyrosine kinase inhibitors (TKIs) and other cancer treatments must, therefore, undergo continuous improvement. Currently, fourth-generation tyrosine kinase inhibitors (TKIs) that act allosterically against the C797S mutation are the most widely used class of medications that target EGFR mutations. To help researchers better understand how to optimize pyrazole and pyrazoline-based derivatives as antiproliferative agents, this review summarises the work done in the last fifteen years on different anti-cancer agents representing 31 most potential compounds along with their activity characteristics, with a particular emphasis on the structure-activity relationship (SAR) of possible pyrazole and pyrazoline derivatives as EGFR tyrosine kinase inhibitors.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011583","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":"Expanding Therapeutic Horizons with Indazole-Based Compounds: A Review of Anticancer, Antimicrobial, and Neuroprotective Applications.","authors":"Pooja Dinkar Bhane, Sarita Suryabhan Pawar","doi":"10.2174/0115734064371097250403114905","DOIUrl":"https://doi.org/10.2174/0115734064371097250403114905","url":null,"abstract":"<p><p>Indazole-based compounds have recently developed and physiologically evaluated as diverse agents for antibacterial, anticancer, anti-inflammatory, anti-obesity, and neurological therapies. This review highlights these advancements. Through molecular docking and experimental tests, scientists have created distinct indazole analogs that exhibit significant inhibitory effects on various biological targets, including 1,2,3-triazolyl-indazoles, carbothioamides, and carboxamides. Key compounds have demonstrated strong bactericidal and antifungal properties against microbes such as S. epidermidis, P. aeruginosa, E. coli, and C. albicans; their effectiveness was enhanced by halogenated and electron-withdrawing substituents. In models including positive HER2 breast cancer and hepatocellular tumors, indazole derivatives have shown efficacy against targets such as CDK2, EGFR, c-Met, HSP90, and VEGFR2 in oncology, resulting in successful anticancer responses. The pharmacokinetics, solubility, and specificity of these compounds have been further improved through structural alterations, such as piperazine ring modifications and C-terminal changes. Additionally, the LRRK2 antagonist MLi-2 demonstrated remarkable efficacy in treating neurodegenerative diseases, while indazole-5-carboxamides exhibited a strong affinity for monoamine oxidases, potentially offering new therapeutic options for Parkinson's disease. Inhibition of COX-2 and FGFR resulted in anti-inflammatory effects, with minimal off-target damage observed in vivo. Collectively, our findings underscore the therapeutic versatility of indazole frameworks across various disease pathways, suggesting their potential for developing innovative treatments for cancer, infections, metabolic disorders, and neurological conditions.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017761","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":"Pyrimidine-Based Compounds in Tuberculosis Management: A Review of their Biological and Medicinal Importance.","authors":"Deepshikha Singh, Vikram Singh, Afrasim Moin, Manu G, B C Revanasiddappa, Sheshagiri R Dixit","doi":"10.2174/0115734064364791250314135438","DOIUrl":"https://doi.org/10.2174/0115734064364791250314135438","url":null,"abstract":"<p><p>Pyrimidine derivatives are a class of chemically & biologically active heterocyclic compounds promising for developing anti-tubercular, anti-viral, anti-malarial, anti-inflammatory, and enzyme-inhibiting drugs. To cure TB, scientists were driven to establish novel pyrimidine derivatives. The main objective of the current review is to identify and develop new pyrimidine moietycontaining derivatives that have been assessed for their structure-activity relationship (SAR). The emergence and widespread spread of several drug-resistant MTB infections, which renders firstline anti-TB medications more ineffective. It is crucial to develop new anti-TB drugs that are extremely effective against both drug-sensitive and drug-resistant TB. The development of pyrimidine therapeutics methods will thus benefit from the current review. Three medications-GSK-286, TBA- 7371, and SPR-720 are now undergoing clinical testing. This study aims to emphasize the structural variety of anti-tuberculosis pyrimidine-containing compounds by providing an overview of current developments in drug discovery investigations.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700629","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 De Novo 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":"https://doi.org/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>Method: </strong>A thorough combination of machine learning (ML) and physics-based methods was employed to achieve these goals, encompassing de novo 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":""},"PeriodicalIF":1.9,"publicationDate":"2025-03-13","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":"Synergistic Warriors: Design and Synthesis of Dual-Acting Schiff-Based Threaded 1,2,3-Triazole Hybrids for Potent Antineoplastic and Anti-Mycobacterial Activities.","authors":"Vinayak Walhekar, Raghavendra Kulkarni, Mohana Vamsi Nuli, Anil Kumar Garige, Dharmesh Deore, Ritesh Pawar, Ashwini Patil, Bhikshapathi Dvrn, Karajagi Santosh, Ravindra Kulkarni","doi":"10.2174/0115734064318062250206104355","DOIUrl":"https://doi.org/10.2174/0115734064318062250206104355","url":null,"abstract":"<p><strong>Objective: </strong>In the pursuit of identifying divergent scaffolds for potential anticancer and anti-mycobacterial agents, a novel series of Schiff-based threaded 1,2,3-triazoles was designed and synthesized.</p><p><strong>Methods: </strong>In this study, novel Schiff-based threaded 1,2,3-triazoles have been meticulously crafted and synthesized. Chemical structures of the synthesized molecules were confirmed by 1H NMR, 13C NMR and Mass spectra. Synthetic analogs were further evaluated for their antiproliferative, antitubercular and antimicrobial potentials by in vitro assays.</p><p><strong>Results: </strong>The in vitro anti-tumor (anti-proliferative) evaluation on HT29 cancer cells revealed that compounds 8b and 8h exhibited remarkable inhibitory activity with IC50 values of 25±0.8 and 24±0.9 μM. In the context of anti-mycobacterial analysis, compound 8c demonstrated promising activity (6.25 μM) against Mycobacterium tuberculosis H37Rv. Moreover, compounds 8d and 8e displayed equipotent antimicrobial potential (3.12 μM) comparable to Ciprofloxacin against both Staphylococcus aureus and Escherichia coli. Molecular docking studies unveiled that 8c exhibited robust binding within the active pocket of carbonic anhydrase XII (docking energy -8.4 kcal/mol) and demonstrated a promising docking profile with β-ketoacyl ACP synthase I (docking energy - 9.5 kcal/mol) in the enzyme's binding pocket.</p><p><strong>Conclusion: </strong>Structure-activity relationship (SAR) analysis identified three pivotal pharmacophores; 1,2,3-triazole, aromatic ring system (substituted with halogens and -NO2), and imine functionalities as crucial for the development of dual inhibitors targeting cancer and tuberculosis, showcasing an outstanding in silico ADMET profile. Therefore, these compounds merit consideration as noteworthy pharmacological lead molecules in the realm of cancer and tuberculosis drug discovery and development.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414648","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 Paşahan, Özlem Demirci, Irmak İçen Taşkın, Aziz Paşahan, Meryem Rüveyda Sever, Yetkin Gök, Aydın Aktaş","doi":"10.2174/0115734064331622241113032042","DOIUrl":"https://doi.org/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 HCT116 (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 SH-SY5Y 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":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-11","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}