Future medicinal chemistry最新文献_第9页

Latest developments in photosensitizers: improving stability, specificity and responsiveness. 光敏剂的最新发展：提高稳定性、特异性和响应性。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-06-01 Epub Date: 2025-06-06 DOI: 10.1080/17568919.2025.2515813

Jiapeng Dong, Jiacheng Tang, Xinyi Li, Yaoxun Zeng, Xiang Su, Yan He, Xujie Liu

{"title":"Latest developments in photosensitizers: improving stability, specificity and responsiveness.","authors":"Jiapeng Dong, Jiacheng Tang, Xinyi Li, Yaoxun Zeng, Xiang Su, Yan He, Xujie Liu","doi":"10.1080/17568919.2025.2515813","DOIUrl":"10.1080/17568919.2025.2515813","url":null,"abstract":"Photodynamic therapy (PDT) has emerged as a promising anticancer strategy utilizing photosensitizers (PSs) to generate cytotoxic reactive oxygen species (ROS) upon light irradiation. This review highlights recent advancements in optimizing PSs through structural modifications, nanocarrier systems, and stimulus-responsive designs, aiming to enhance their stability, specificity, and responsiveness. Key strategies include chemical modifications (e.g. D-A type structures, shortening the polymethine chain or incorporation of rigid cyclic segments, etc.), nanocarrier encapsulation (e.g. extracellular vesicles and liposomes), host-guest interactions, and specific targeting mechanisms (e.g. organelle-specific localization, antibody conjugation). Additionally, the responsiveness to tumor microenvironment (TME) factors, such as glutathione levels, viscosity, pH, and ROS, has been leveraged to improve the precision and minimize off-target toxicity. Despite significant progress, challenges persist in balancing photostability, biocompatibility, and clinical translatability, highlighting the need for continued innovation in PS design.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1297-1314"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effectiveness of 3-amino-2-thiocyanato-α, β-unsaturated carbonyl compounds against chikungunya virus. 3-氨基-2-硫氰酸酯-α， β-不饱和羰基化合物对基孔肯雅病毒的有效性。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-06-01 Epub Date: 2025-06-13 DOI: 10.1080/17568919.2025.2517527

Kalichamy Alagarasu, Radhika Dhote, Pooja K Bagad, Dwidhesh Kharikar, Poonam Patil, Diya Roy, Shridhar Shukla, Sarah Cherian, Beeran Senthilkumar, Deepti Parashar

{"title":"Effectiveness of 3-amino-2-thiocyanato-α, β-unsaturated carbonyl compounds against chikungunya virus.","authors":"Kalichamy Alagarasu, Radhika Dhote, Pooja K Bagad, Dwidhesh Kharikar, Poonam Patil, Diya Roy, Shridhar Shukla, Sarah Cherian, Beeran Senthilkumar, Deepti Parashar","doi":"10.1080/17568919.2025.2517527","DOIUrl":"10.1080/17568919.2025.2517527","url":null,"abstract":"Aim: Chikungunya fever (CHIKF) caused by the chikungunya virus (CHIKV) is characterized by the presence of long-term polyarthralgia in a minor proportion of the infected patients. Currently, there are no FDA-approved antivirals available. This study evaluated the anti-CHIKV potential of 16 synthetic 3-amino-2-thiocyanato-α, β-unsaturated carbonyl compounds and elucidated their probable mechanisms of action.Methods: Anti-CHIKV activity of 16 compounds were investigated in Vero CCL-81 cells using focus forming unit assay (FFU). Dose-dependent and time-dependent antiviral assays were performed for the effective compounds. Molecular docking was performed to find out their interactions with viral proteins.Results: Five compounds showed promising anti-CHIKV activity by reducing viral titer with >1 log10 FFU/ml. Dose-dependent studies revealed that the compound 3 g was more effective in reducing the virus titer with a half-maximal inhibitory concentration (IC50) of 0.4315 μM and a selectivity index of 35.99. Docking analyses revealed that all the compounds mainly interact with the non-structural proteins of CHIKV.Conclusions: These findings demonstrate the in vitro anti-CHIKV activity of these compounds, and their possible mode of action via interference with early stages of infection and replication processes. This study warrants further preclinical and clinical evaluation to establish their safety and efficacy as novel anti-CHIKV therapeutics.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1269-1279"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The current status of quinazoline hybrids with antibreast cancer therapeutic potential-part II. 喹唑啉杂合物抗乳腺癌治疗潜力的研究现状（二）。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-06-01 Epub Date: 2025-06-06 DOI: 10.1080/17568919.2025.2515816

Huanhong Zeng, Minxue Zhuang, Feili Cai, Mengbo Lin, Ruo Wang, Jiawen Wang, Hui Zhang

{"title":"The current status of quinazoline hybrids with antibreast cancer therapeutic potential-part II.","authors":"Huanhong Zeng, Minxue Zhuang, Feili Cai, Mengbo Lin, Ruo Wang, Jiawen Wang, Hui Zhang","doi":"10.1080/17568919.2025.2515816","DOIUrl":"10.1080/17568919.2025.2515816","url":null,"abstract":"Breast cancer, characterized by the unchecked proliferation of breast cells, which usually leads to invasive behaviors and metastatic spread, is a pervasive and multifaceted disease and remains the foremost cause of death in women across the world. Tens of chemotherapeutics have already been approved for breast cancer therapy, but multidrug resistance and severe side effects have increased both mortality and morbidity as a consequence of treatment failures, creating an urgent need to develop novel chemotherapeutics. Quinazoline hybrids with structural variations could affect breast cancer in distinct manners and have the potential to enhance efficacy, reduce side effects, and address multidrug resistance. Moreover, several quinazoline hybrids, which are exemplified by tucatinib and lapatinib, have already been applied in clinics for the treatment of breast cancer, revealing that quinazoline hybrids are valuable entities for the exploitation of novel antibreast cancer chemotherapeutics. This review outlines the current status of quinazoline hybrids with antibreast cancer potential, covering articles published from 2020 onwards. The structure-activity relationships (SARs) and mechanisms of action are also discussed to provide a potential avenue for developing more effective antibreast cancer candidates.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1457-1469"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The current landscape of indole hybrids with in vivo antitumor potential. 具有体内抗肿瘤潜力的吲哚杂合体的现状。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-06-01 Epub Date: 2025-07-16 DOI: 10.1080/17568919.2025.2521250

He Ling, Zhu Congcong

引用次数: 0

Synthesis, antiproliferative evaluation and in silico studies of new quinazoline derivatives as VEGFR-2 inhibitors. 新的喹唑啉衍生物作为VEGFR-2抑制剂的合成、抗增殖评价和硅片研究。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-06-01 Epub Date: 2025-07-04 DOI: 10.1080/17568919.2025.2525073

Abdelsalam Mohamed Abdelsalam Ouf, Adel A Marzouk, Montaser Sh A Shaykoon, Ismail Celik, Dina A Bakhotmah, Ahd A Mansour, Mariam K Alamoudi, Abdallah M Alfayomy, Mohamed Ayman El-Zahabi

{"title":"Synthesis, antiproliferative evaluation and in silico studies of new quinazoline derivatives as VEGFR-2 inhibitors.","authors":"Abdelsalam Mohamed Abdelsalam Ouf, Adel A Marzouk, Montaser Sh A Shaykoon, Ismail Celik, Dina A Bakhotmah, Ahd A Mansour, Mariam K Alamoudi, Abdallah M Alfayomy, Mohamed Ayman El-Zahabi","doi":"10.1080/17568919.2025.2525073","DOIUrl":"10.1080/17568919.2025.2525073","url":null,"abstract":"Background: New quinazoline derivatives were designed and synthesized to target VEGFR-2, aiming to identify potential anticancer agents.Research design and methods: The synthesized compounds underwent in vitro screening to evaluate their cytotoxic effects across 60 cancer cells following the NCI protocol. The most promising derivatives, 3i and 3j, underwent further evaluation via a five-dose test to assess broad-spectrum anticancer activity. Their VEGFR-2 inhibitory potential was compared to sorafenib. Cell cycle analyses, annexin V-FITC, and apoptotic markers were used to examine HT-29 colon cancer cells after treatment with 3j for cell cycle arrest and apoptosis induction. Molecular docking and MD simulations explored binding interactions, while ADMET studies assessed pharmacokinetics.Results: Compounds 3i and 3j exhibited potent to moderate cytotoxic activity, with compound 3j showing the highest activity against colon cancer cell lines (GI50 = 3.29 μM). Both compounds demonstrated promising VEGFR-2 inhibitory activity (IC50 = 0.120 and 0.197 µM, respectively), comparable to sorafenib (IC50 = 0.088 µM). Cell cycle analysis displayed G1 phase arrest and pro-apoptotic effects. Docking studies confirmed favorable VEGFR-2 binding affinity (-7.57 and -7.83 kcal/mol). ADMET profiling indicated promising drug-like properties.Conclusions: Compounds 3i and 3j exhibit promising VEGFR-2 inhibitory properties and significant anticancer activity, warranting further investigation.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1407-1422"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New and potential boron-containing compounds for treatment of Alzheimer's disease and cancers. 用于治疗阿尔茨海默病和癌症的新型和潜在含硼化合物。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-06-01 Epub Date: 2025-07-02 DOI: 10.1080/17568919.2025.2525065

Ferah Comert Onder, Kadircan Ural, Alper Onder, Bulent Ozpolat, Mehmet Ay

{"title":"New and potential boron-containing compounds for treatment of Alzheimer's disease and cancers.","authors":"Ferah Comert Onder, Kadircan Ural, Alper Onder, Bulent Ozpolat, Mehmet Ay","doi":"10.1080/17568919.2025.2525065","DOIUrl":"10.1080/17568919.2025.2525065","url":null,"abstract":"Aim: In this study, new boron-containing carbamate compounds were synthesized and evaluated as potential acetylcholinesterase (AChE) inhibitors by in vitro and in silico analyses.Materials & methods: The structures were characterized by spectroscopic analysis including 1H NMR, 13C NMR, 11B NMR, and MS. The purities of the compounds were determined by HPLC analysis. In vitro and in silico analyses were performed.Results: Based on our findings, compounds (1-4) demonstrated more potent AChE inhibitory activity compared to tacrine, which is an FDA-approved AChE inhibitor. Compound 4 had the highest inhibitory activity with an IC50 of 37.87 ± 0.96 nM and was more effective than tacrine (74.23 ± 0.83 nM). Compounds 1, 2, and 3, respectively, showed 1.78-, 1.73-, and 1.58-fold more potent enzyme inhibition activity compared to tacrine. The strong interactions with critical residues in the binding pocket of AChE were identified between protein and the compounds. Furthermore, compound 4 exerted an antiproliferative activity against various human cancer cell lines (32.91 ± 4.92 µM in HT29 and 42.38 ± 2.73 µM in MCF-7).Conclusion: Our study indicates the discovery of new boron-containing AChE inhibitors as potential candidates for the treatment of Alzheimer's disease and cancer.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1377-1389"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The current landscape of quinazoline derivatives with in vivo anticancer therapeutic potential-part I. 具有体内抗癌治疗潜力的喹唑啉衍生物的现状-第一部分。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-06-01 Epub Date: 2025-06-05 DOI: 10.1080/17568919.2025.2515818

Shijia Zhao, Yan Zhang, Zhi Xu

{"title":"The current landscape of quinazoline derivatives with in vivo anticancer therapeutic potential-part I.","authors":"Shijia Zhao, Yan Zhang, Zhi Xu","doi":"10.1080/17568919.2025.2515818","DOIUrl":"10.1080/17568919.2025.2515818","url":null,"abstract":"With the development of new technology, cancer has already transformed from a catastrophic disease to a treatable and sometimes curable disease. Chemotherapeutics is critical for cancer therapy, but multidrug resistance and severe side effects often lead to treatment failure, creating an urgent demand to develop innovative and efficient therapeutic interventions. Quinazoline hybrids could arrest the cell cycle, induce apoptosis, inhibit angiogenesis, and disrupt cell migration. Moreover, several quinazoline hybrids, exemplified by Fruquintinib (quinazoline-benzofuran hybrid) and Barasertib (quinazoline-pyrazole hybrid), have already been applied in clinics for cancer therapy, indicating that the rational design of quinazoline hybrids may provide valuable chemotherapeutics for cancer therapy. This review outlines the current scenario of the in vivo anticancer therapeutic potential of quinazoline hybrids, together with modes of action, toxicity, and pharmacokinetic properties, developed from 2015 onwards, aiming to provide promising candidates for further preclinical/clinical evaluations and to facilitate further rational design.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1281-1295"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis, antioxidant activity of novel sulfonamide and sulfonate organic salts bearing various heterocyclic moieties. 含各种杂环基团的新型磺胺类及磺胺类有机盐类的合成及其抗氧化活性。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-06-01 Epub Date: 2025-07-01 DOI: 10.1080/17568919.2025.2517529

Didier Forest Kouganou Djossu, Joseph Tsemeugne, Paul Etoga Mbarga, Jean-De-Dieu Tamokou, Germaine Takongmo Matsuete, Armelle Tontsa Tsamo, Valerie Tedjon Sielinou, Edwin Mpho Mmutlane, Pierre Mkounga, Dieter Schollmeyer, Emmanuel Fondjo Sopbué, Augustin Ephrem Nkengfack

{"title":"Synthesis, antioxidant activity of novel sulfonamide and sulfonate organic salts bearing various heterocyclic moieties.","authors":"Didier Forest Kouganou Djossu, Joseph Tsemeugne, Paul Etoga Mbarga, Jean-De-Dieu Tamokou, Germaine Takongmo Matsuete, Armelle Tontsa Tsamo, Valerie Tedjon Sielinou, Edwin Mpho Mmutlane, Pierre Mkounga, Dieter Schollmeyer, Emmanuel Fondjo Sopbué, Augustin Ephrem Nkengfack","doi":"10.1080/17568919.2025.2517529","DOIUrl":"10.1080/17568919.2025.2517529","url":null,"abstract":"Aim: The reactions of various heterocyclic primary amines with sulfonyl chloride derivatives or with sulfosalicylic acid results in the first case to the formation of sulfonamide derivatives and in the second case to the formation of sulfonate organic salts which are both hybrid molecule that integrate multiple pharmacophores into a single scaffold.Materials and methods: The novel sulfonamide derivatives 3 were obtained through mono-nucleophilic addition reactions of the corresponding primary amines to the appropriate sulfonyl derivative. In contrast, the sulfonate organic salts 5, 7 and 8 were formed as the result of an acid-base neutralization reaction, during which a molecule of amine captures the acid proton from the sulfosalicylic acid molecule. The antioxidant activity of the synthesized compounds is evaluated by determining their DPPH (2,2-Diphenyl-1-picrylhydrazyl) free radical scavenging activity as well as gallic acid equivalent antioxidant capacity (GEAC).Results and conclusion: The structures of compounds 3, 5, 7 and 8 were confirmed through elemental analysis, IR (Infrared), UV-Vis (ultraviolet-visible), 1H-NMR (Proton nuclear magnetic resonance), 13C-NMR (Carbon-13 nuclear magnetic resonance) and HRMS (High-Resolution Mass Spectrometry) spectroscopic data. Organic salt 7a was characterized by single-crystal and X-ray diffraction. Organic sulfonate salts were found to be more active than covalent sulfonamide derivatives.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1259-1268"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Repurposing sulfonamide-scaffolds for enhanced and sustainable malaria therapy. 重新利用磺胺支架加强和可持续的疟疾治疗。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-06-01 Epub Date: 2025-06-27 DOI: 10.1080/17568919.2025.2515819

Durga Prasad Mishra, Roja Sahu, Prafulla Kumar Sahu, Sipra Ghadai, Arin Kumar Padhan, Tapash Kumar Sahu, Satyabrata Naik, Biswajeet Acharya

{"title":"Repurposing sulfonamide-scaffolds for enhanced and sustainable malaria therapy.","authors":"Durga Prasad Mishra, Roja Sahu, Prafulla Kumar Sahu, Sipra Ghadai, Arin Kumar Padhan, Tapash Kumar Sahu, Satyabrata Naik, Biswajeet Acharya","doi":"10.1080/17568919.2025.2515819","DOIUrl":"10.1080/17568919.2025.2515819","url":null,"abstract":"Malaria continues to pose a significant global health burden, with an estimated 263 million cases and 597,000 deaths reported in 2023, disproportionately affecting the WHO African Region. The emergence of drug-resistant Plasmodium strains has necessitated the search for novel therapeutic strategies. Sulfonamides, originally introduced as antibacterial agents, have been repurposed as promising antimalarial compounds due to their unique mechanism of action. These compounds inhibit the dihydropteroate synthase (DHPS) enzyme in the folate biosynthesis pathway, a critical process for DNA, RNA, and protein synthesis in Plasmodium species. By acting as competitive alternative to para-aminobenzoic acid (PABA), sulfonamides disrupt parasite replication and survival. Advances in structure-activity relationship studies have led to the development of sulfonamide derivatives with improved binding affinity, pharmacokinetic properties, and reduced toxicity. Combination therapies, such as sulfadoxine-pyrimethamine, exploit the synergistic inhibition of the folate pathway to enhance efficacy and mitigate resistance. This review highlights the mechanistic insights, structural advancements, and clinical applications of sulfonamide-based antimalarials, emphasizing their role in sustainable malaria control, particularly in combating multidrug-resistant strains of Plasmodium.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1315-1335"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel thiazole-thiadiazole as a potential anti-Alzheimer agent: synthesis and molecular interactions via an in silico study. 新型噻唑-噻二唑作为潜在的抗阿尔茨海默病药物：通过硅研究的合成和分子相互作用。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-06-01 Epub Date: 2025-07-03 DOI: 10.1080/17568919.2025.2525066

Shoaib Khan, Tayyiaba Iqbal, Rafaqat Hussain, Zanib Fiaz, Magda H Abdellattif, Hamdy Kashtoh

{"title":"Novel thiazole-thiadiazole as a potential anti-Alzheimer agent: synthesis and molecular interactions via an in silico study.","authors":"Shoaib Khan, Tayyiaba Iqbal, Rafaqat Hussain, Zanib Fiaz, Magda H Abdellattif, Hamdy Kashtoh","doi":"10.1080/17568919.2025.2525066","DOIUrl":"10.1080/17568919.2025.2525066","url":null,"abstract":"Aim: This study aimed to synthesize and evaluate a series of thiazole-derived thiadiazole-based Schiff base derivatives (1-16) for their potential anti-Alzheimer and antioxidant activities, with a focus on identifying promising drug-like candidates.Materials & methods: The synthesized compounds were structurally characterized using 1H-NMR, 13C-NMR, and mass spectrometry. Their biological potential was assessed via in vitro anti-Alzheimer assays (AChE and BuChE inhibition) and DPPH-based antioxidant screening. Molecular docking was employed to predict binding interactions with relevant protein targets. Additionally, ADMET profiling was carried out to evaluate pharmacokinetic and toxicity parameters.Results: Among the tested compounds, derivative 8, bearing a trifluoromethyl substitution, showed the most potent activity against Alzheimer-related enzymes, surpassing the standard drug donepezil. Derivatives 3, 7, and 12 also exhibited significant bioactivity. Docking studies confirmed strong binding affinities of the active compounds to key residues within the enzyme active sites. ADMET analysis indicated favorable drug-likeness and safety profiles.Conclusions: The synthesized Schiff-base derivatives, especially compound 8, demonstrated strong anti-Alzheimer and antioxidant activity. These findings suggest their potential as lead candidates for further development of multifunctional therapeutics targeting neurodegenerative disorders.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1349-1361"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0