Medicinal Chemistry最新文献

{"title":"Effective Synthesis of Dopamine Dimer.","authors":"Zhou Dejun, Zhang Yuying, Liu Xiaoyue, Zheng Huachuan","doi":"10.2174/0115734064262975241208063806","DOIUrl":"10.2174/0115734064262975241208063806","url":null,"abstract":"<p><strong>Background: </strong>Dopamine (1) is a commonly used vasopressor, primarily employed to treat various types of shock, congestive heart failure, and acute renal failure. Dopamine dimer (2) is an impurity generated during the production process of dopamine raw materials or the metabolism of dopamine drugs themselves.</p><p><strong>Methods: </strong>This article presents an effective method for synthesizing dopamine dimer through the condensation of methyl 3,4-dimethoxyphenyl acetate (4) and 3,4-dimethoxyphenylethyl amine (5), followed by reduction and demethylation.</p><p><strong>Results: </strong>The product was synthesized from easily accessible raw materials, achieving a total yield of 48% over five steps.</p><p><strong>Conclusion: </strong>This synthesis method is simple and beneficial for pharmaceutical companies to adopt and implement.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"67-72"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033447","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":"Heterocyclic Derivatives in Parkinson's Therapy: Recent Advances and Prospects.","authors":"Kanupriya, Vikram Sharma, Suraj Pal Verma, Isha Mishra, Ravi Kumar Mittal, Tanya Biswas, Raghav Mishra","doi":"10.2174/0115734064329778240930084333","DOIUrl":"10.2174/0115734064329778240930084333","url":null,"abstract":"<p><p>The aim of this study is to conduct a thorough examination of the most recent derivatives that have been studied for their potential in treating Parkinson's disease and to establish the connection between the chemical structure of these derivatives and their effectiveness as therapeutic agents. A thorough examination of the available literature was carried out to gather data about the identification of pertinent research on derivatives aimed at addressing Parkinson's disease. The literature was analyzed to determine derivative chemical structures, modes of action, and preclinical and clinical results. To discover novel derivatives with therapeutic potential for Parkinson's disease, our investigation uncovered a variety of such chemical compounds. These derivatives cover a wide range of chemical classes and demonstrate different ways of working, such as impacting neurotransmitter systems, acting as antioxidants, and providing neuroprotective effects. In addition, an examination of the SAR (Structure-activity relationship) uncovered important structural characteristics linked to improved therapeutic effectiveness. This manuscript offers a thorough examination of the most recent derivatives aimed at addressing Parkinson's disease and their potential for therapeutic use. The understanding of SAR and pharmacological attributes provides insights into the development and refining of novel medications for Parkinson's disease treatment, promoting advancement in the field of neurotherapeutics.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"22 2","pages":"113-126"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839931","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":"Syntheses and Identification of New Dithiophosphinic Acid Complexes and their Potential as Photodynamic Agents in Cancer Therapy.","authors":"Kubra A Coskun, Elif Bulat, Hamza Yılmaz, Ertugrul Gazi Saglam, Lutfi Tutar, Fayyaz Ur Rehman, Yusuf Tutar","doi":"10.2174/0115734064382461250618113452","DOIUrl":"10.2174/0115734064382461250618113452","url":null,"abstract":"<p><strong>Background: </strong>The photo-efficacy of oncological phototherapy for both internal and external tumors is encouraging. When light and photochemotherapeutic drugs are applied together, precise cancer targeting, minimal invasiveness, and innovative modes of action are made possible. Current developments in photoactive compounds and new light sources are promising for further advancement.</p><p><strong>Objective: </strong>When designing photosensitizers, metal complexes may be advantageous since the metal can enhance stability and photocytotoxicity while facilitating their localization and quantification. The absorption spectra of photosensitizers limit their excitation wavelengths, which impact light tissue penetration that differs in various organs. Since longer wavelength light penetrates deeper, PDT is typically carried out at wavelengths greater than 620 nm. Additionally, employing lower intensity (>4-8 J/cm²) energy can greatly lessen the pain and discomfort induced by red-light PDT.</p><p><strong>Methods: </strong>Low-level laser therapy exposure was used to assess the dithiophosphinic acid complexes' photodynamic treatment efficacy in MCF-7 cells. Following the administration of the complexes at concentrations within IC₅₀ values, red light (4 J, 780 nm) was applied to the cells. Afterward, MCF-7 cells were cultured for 24 hours to evaluate the photodynamic effects of the compounds on cancer cells. Cell viability was assessed using the XTT assay kit.</p><p><strong>Results: </strong>DTPA complexes have shown effectiveness as photodynamic agents in cancer therapy, with Ni(II) and Ni(II)-pyridine complexes demonstrating significant cytotoxicity against cancer cells.</p><p><strong>Conclusion: </strong>Light-activated cancer cell therapies are promising, and the synthesized complexes affect the cell cycle and apoptosis-regulating proteins. The compounds can be employed as anticancer agents and a fine starting template for photodynamic drug design.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"361-375"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575788","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":"Unlocking the Biological Potential of 2-Pyridones: Synthesis, Antioxidant and Antimicrobial Activity of N-Phenacylated 5/6-Chloro-2-pyridones.","authors":"Sarita Sangwan, Sonu Chauhan, Neelam Yadav, Ravi Kumar, Anil Duhan, Vinod Malik, Jayant Sindhu","doi":"10.2174/0115734064336556250116195638","DOIUrl":"10.2174/0115734064336556250116195638","url":null,"abstract":"<p><strong>Aims: </strong>A simple and efficient synthesis of 14 new (9a-9n) N-phenacyl-2-pyridones with good yields (up to 75%), is reported. The synthesized derivatives were screened for their in vitro radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), their in vitro antimicrobial potential was tested against human pathogenic bacterial strains, including <i>Bacillus cereus, Staphylococcus aureus, Escherichia coli</i>, and <i>Pseudomonas aeruginosa</i>, as well as the fungal strain Candida albicans.</p><p><strong>Methods: </strong>All compounds displayed modest antioxidant activity, with compound 9b being the most potent in the DPPH radical scavenging assay. Most of the synthesized compounds exhibited good to excellent antimicrobial activity, however, the compounds (9d, and 9b) showed maximum inhibition zone diameters of 18.75, and 18.25 mm respectively, demonstrating better antimicrobial potential than the standard drug streptomycin against <i>Staphylococcus aureus</i>.</p><p><strong>Results: </strong>Compound 9f was found most effective against <i>Pseudomonas aeruginosa</i> with a 23.25 mm zone of inhibition against a 17.50 mm zone of inhibition of the standard, streptomycin. Molecular docking of the compounds 9d and 9f with tyrosyl-tRNA synthetase revealed good binding with the target.</p><p><strong>Conclusion: </strong>The electron-withdrawing substituents on the aryl ring of synthesized N-phenacyl-2- pyridones improved the antioxidant activity, however, for Gram-positive bacteria, less lipophilic or more hydrophilic substituents, such as halogens, displayed better antimicrobial activity. Similarly, it was the more lipophilic substitutions on the aryl ring that improved the antimicrobial activity against Gram-negative bacteria.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"73-82"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414687","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":"Bioactive Compounds from <i>Myrica esculenta</i>: Antioxidant Insights and Docking Studies on H⁺K⁺-ATPase and H₂ Receptor Targets.","authors":"Rashmi Pathak, Phool Chandra","doi":"10.2174/0115734064366819250125070619","DOIUrl":"10.2174/0115734064366819250125070619","url":null,"abstract":"<p><strong>Background: </strong><i>Myrica esculenta</i> (Myricaceae) are common in the Indian Himalayas. Traditional medicine uses it to treat chronic bronchitis, inflammation, stomach ulcers, anaemia, diarrhoea, asthma, and ear, throat, and nose disorders. Its varied medicinal benefits are recognised in the ayurvedic pharmacopoeia.</p><p><strong>Aims: </strong>Isolation of Bioactive Compounds from M. esculenta: Assessment of Antioxidant Activity and Molecular Docking Studies Targeting the H⁺K⁺-ATPase enzyme and H₂ Receptor.</p><p><strong>Materials and methods: </strong>The fruit of the Myrica esculenta plant was extracted. The total phenolic and total flavonoid content of the extract were determined. Following column chromatography, two phytoconstituents were identified by mass spectroscopy, FTIR, and NMR. The antioxidant activity of phytoconstituents was evaluated using the DPPH Scavenging Assay, Reactive Nitrogen Oxide Scavenging Assay, and Hydroxyl Free Radical Scavenging Assay. Then, molecular docking studies were performed against the H⁺K⁺-ATPase enzyme and H₂ Receptor.</p><p><strong>Results: </strong>The research successfully extracted methanolic extract from M. esculenta by maceration, which yielded rich in flavonoids and phenolic content and isolated compounds using column chromatography, which was further characterized to be myricetin and catechin using Mass spectroscopy, FTIR, and NMR. The further evaluation of the antioxidant activity of compounds demonstrated significant activity with IC₅₀ value indicating strong free radical scavenging activity. Molecular docking studies were performed against the H⁺K⁺-ATPase enzyme and H₂ Receptor, revealing that both the compounds exhibit high binding affinity and favorable interactions with key sites.</p><p><strong>Conclusion: </strong>The findings suggest that the isolated compounds myricetin and catechin possess potential antioxidant activity and could be a potential therapeutic target for the H⁺K⁺-ATPase enzyme and H₂ Receptor.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"83-98"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364926","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":"Identification of Potential Dual HDAC6 and HSP90 Inhibitors for the Treatment of Cancer using Molecular Docking, Molecular Dynamics and MM/PBSA Studies: A Comprehensive <i>In Silico</i> Study.","authors":"Muhsin Samet Yucel, Ismail Akcok","doi":"10.2174/0115734064388900250625121927","DOIUrl":"10.2174/0115734064388900250625121927","url":null,"abstract":"<p><strong>Background: </strong>Histone deacetylase 6 (HDAC6) and heat shock protein 90 (Hsp90) are crucial therapeutic targets in cancer research with their interconnected roles in regulating protein homeostasis and cellular processes. The interaction of these proteins within the cytosolic complex plays a critical role in regulating cancer cell survival and progression. Notably, current studies highlight that the simultaneous inhibition of HDAC6 and Hsp90 can produce synergistic effects and offer a promising therapeutic potential for combating malignant cancers.</p><p><strong>Objective: </strong>The objective of this study was to explore potential compounds that can inhibit both HDAC6 and Hsp90 proteins.</p><p><strong>Methods: </strong>In this study, a number of in-silico computational techniques were employed. A total of 791 molecules, sharing at least 30% similarity with previously identified four HDAC inhibitors, were obtained from the ZINC15 database and subjected to docking on HDAC6 and Hsp90 proteins. The top eight ligands demonstrating the best binding scores against both targets, with panobinostat and ganetespib serving as reference compounds for HDAC6 and Hsp90, respectively, were selected for further analysis. Subsequently, ADME prediction and molecular dynamics simulations were conducted on the selected ligands.</p><p><strong>Results: </strong>A detailed molecular docking, molecular dynamics simulations and ADME studies have revealed that ZINC27653366 exhibited the highest inhibitory potential against both Hsp90 and HDAC6 target proteins, making it the most promising inhibitor.</p><p><strong>Conclusion: </strong>In conclusion, although additional in vitro and in vivo studies are required for the validation, in silico evaluation of ZINC27653366 may position it as a promising candidate for the treatment of different types of cancers.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"212-229"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584310","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":"Research Progress of G Protein-coupled Receptor 52 on Central Nervous System Diseases.","authors":"Qingkun Wu, Jun Li, Xiaojie Hu, Ying Zhuang, Lu Zheng","doi":"10.2174/0115734064372441250527031957","DOIUrl":"10.2174/0115734064372441250527031957","url":null,"abstract":"<p><p>The G protein-coupled receptor 52 (GPR52) is a Gs-coupled receptor and is located principally in the striatum alongside D₂ receptor and in the pre-frontal cortex alongside D₁ receptor. Its stimulation leads to potentiation of intracellular cAMP levels, producing effects on cAMP levels similar to those of a Gi-coupled D₂ receptor antagonist in the striatum and a Gscoupled D₁ receptor agonist in the prefrontal cortex. This dual mechanism suggests that GPR52 activation could result in antipsychotic effects akin to D₂ antagonism and pro-cognitive effects resembling D1 agonism. As a result, GPR52 has emerged as a promising therapeutic target for central nervous system (CNS) disorders, including schizophrenia and substance use disorder. Additionally, knocking out (KO) GPR52 not only significantly reduces mutant huntingtin protein (mHTT) levels in the striatum but also rescues Huntington's disease-associated behavioral phenotypes in a knock-in Huntington's disease mouse model, which provides evidence that GRP52 may also serve as a potential target for Huntington's disease. This review summarizes the current state of small-molecule ligand/drug discovery for GPR52, focusing on the latest findings about the role of GPR52 in schizophrenia and Huntington's disease.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"231-241"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187262","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":"Discovering the Cholinesterase Inhibitory Potential of Thiosemicarbazone Derivatives through <i>In vitro</i>, Molecular Docking, Kinetics, and Dynamics Studies.","authors":"Manel Essid, Aftab Alam, Ghulam Fareed, Sudais Rahman, Imtiaz Ahmad, Imen Zghab, Zainab Hassan Alnakhli, Abid Ali, Masroor Kamal, Momin Khan","doi":"10.2174/0115734064375028250427171931","DOIUrl":"10.2174/0115734064375028250427171931","url":null,"abstract":"<p><strong>Background: </strong>The current study explored the cholinesterase inhibitory activities of some thiosemicarbazone derivatives bearing 2,4-dichloro phenylacetic acid scaffold.</p><p><strong>Objective: </strong>This study aimed to screen the synthesized derivatives for their in vitro acetylcholine and butyrylcholinesterase inhibition.</p><p><strong>Methods: </strong>These compounds were synthesized by refluxing 2,4-dichloro phenylacetic acid with sulfuric acid in ethanol to get the ester, which was further refluxed with thiosemicarbazide in ethanol to get the desired compound (2). Different benzaldehydes were treated with compound (2) in ethanol having a catalytic amount of acetic acid to get thiosemicarbazones.</p><p><strong>Results: </strong>In the series, seven compounds, including compounds 2c, 2a, 2b, 2d, 2g, 2e, and 2f, displayed excellent acetylcholinesterase inhibition activities in the range of IC₅₀ values from 41.51 ± 3.88 to 95.48 ± 0.70 μM, surpassing than the standard galantamine (IC₅₀ = 104.5 ± 1.20 μM). Also, compounds 2a, 2g, 2h, 2f, 2b, and 2d with IC₅₀ values ranging from 64.47 ± 2.74 to 80.62 ± 0.73 μM exhibited potent inhibition against butyrylcholinesterase enzyme, being similar to the standard galantamine (IC₅₀ = 156.8 ± 1.50 μM). The molecular docking investigation was performed to assess the binding affinity of the compounds with the active site of the enzyme. These compounds, along with the docked complexes, specifically AChE-compound 2a and BuChE-compound 2g, were chosen and subjected to 100-nanosecond molecular dynamics simulations. The simulations demonstrated strong stability of the ligands within the active pockets of AChE and BuChE enzymes.</p><p><strong>Conclusion: </strong>These derivatives exhibited superior acetylcholinesterase and butyrylcholinesterase inhibitory activities compared to galantamine, with molecular docking and dynamic simulations confirming their strong binding affinity with the active sites of the enzymes.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"347-360"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028716","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":"Preface.","authors":"Dimitra Hadjipavlou-Litina","doi":"10.2174/0115734064444306250924103523","DOIUrl":"10.2174/0115734064444306250924103523","url":null,"abstract":"","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"v-vi"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199783","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":"Screening of Novel Inhibitors Targeting the Non-ATP-binding Domain of <i>Staphylococcus aureus</i> SecA1.","authors":"Yan Liu, Qing Su, Zonglin Wang, Peiyao Liu, Jinjin Hong, Hyuk-Kyu Seoh, Xu Jia, Sen-Fang Sui, Phang-Cheng Tai, Xinhe Huang","doi":"10.2174/0115734064370398250426162503","DOIUrl":"10.2174/0115734064370398250426162503","url":null,"abstract":"<p><strong>Objective: </strong><i>Staphylococcus aureus (S. aureus)</i> has been one of the pathogenic bacteria for clinical infections, and there is an urgent need for the development of novel anti-S. aureus drugs. SecA is a conserved and essential protein in bacteria and is considered as an ideal target for development. Current screening of inhibitors against SecA has focused on the ATP-binding structural domain, which increases the risk of drug side effects, so a novel screening strategy based on the non-ATP-binding structural domain was chosen in this paper.</p><p><strong>Methods: </strong>A three-dimensional structural model of S. aureus SecA1N75 was constructed, and molecular docking was utilized to screen small molecules with strong interactions with the non- ATP binding domains from a compound library, and four candidate compounds were finally targeted. Molecular dynamics simulations of the candidate molecules were performed to evaluate their drug potential.</p><p><strong>Results: </strong>The four candidate compounds formed stable interactions with key residues of the SecA binding pocket. Molecular dynamics simulations further showed that the candidate molecules bound to the receptor in a stable conformation with nM-level inhibition constants, displaying potent SecA inhibitory activity. It lays the foundation of a lead compound for the development of antimicrobial drugs targeting SecA.</p><p><strong>Conclusion: </strong>In this thesis, an inhibitor screening strategy based on non-ATP binding structural domains was successfully constructed, which breaks through the limitations of traditional methods to screen candidate molecules with high activity and low risk of potential side effects, and provides an innovative solution to meet the challenge of S. aureus drug resistance.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"289-300"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016401","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}