Medicinal Chemistry Research最新文献

{"title":"A glance into Schiff-based α-glucosidase inhibitors in medicinal chemistry","authors":"Sakineh Dadashpour","doi":"10.1007/s00044-025-03390-9","DOIUrl":"10.1007/s00044-025-03390-9","url":null,"abstract":"<div><p>Diabetes mellitus is a chronic disorder characterized by hyperglycemia and is caused by metabolic dysregulation. According to a report from the World Health Organization (WHO), in 2014, more than 422 million people in the world were diagnosed with diabetes. In the small intestine, α-glucosidase mediates the hydrolysis of polysaccharides into monosaccharides which cause a spike in blood glucose levels. Therefore, inhibitors of α-glucosidase can reduce the rate of polysaccharides breakdown, reduce of glucose absorption, and provide antidiabetic effects. Schiff bases derived from a primary amine and carbonyl compound involving an aldehyde or a ketone, are a well-known group of organic compounds with a broad range of biological activities including antidiabetic activity. The current study emphasizes the molecular structure of various synthesized Schiff base-containing compounds and the structure-activity relationship of the most active compounds that serve as α-glucosidase inhibitors. We believe this review will provide valuable information for those developing Schiff base compounds with antidiabetic activity.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 5","pages":"945 - 965"},"PeriodicalIF":2.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919012","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":"Discovery of novel benzbromarone derivatives via the closed metabolic site as potent human uric acid transporter 1 (URAT1) inhibitors","authors":"Wenfeng Ye,&nbsp;Mingchao He,&nbsp;Gaofeng Lin,&nbsp;Li Shao,&nbsp;Jiajia Mo,&nbsp;Yan Zhao,&nbsp;Xiaodong Ma,&nbsp;Qinlong Xu,&nbsp;Zhaoxing Chu","doi":"10.1007/s00044-025-03389-2","DOIUrl":"10.1007/s00044-025-03389-2","url":null,"abstract":"<div><p>Although benzbromarone is a highly potent inhibitor of URAT1, the toxicity of its metabolite has led to the restricted use. In this study, to decrease its toxicity, thirteen benzbromarone derivatives were designed and synthesized via blocking metabolic site. Among them, most of the compounds had moderate to strong inhibitory activity against URAT1, with IC₅₀ values ranging from 0.041 ± 0.010 μM to 3.208 ± 0.458 μM. In particular, compound <b>30</b> demonstrated the most potent URAT1-inhibitory activity (IC₅₀ = 0.041 ± 0.010 μM), which is nearly seven-fold enhanced over BBR (IC₅₀ = 0.278 ± 0.053 μM). Importantly, it displayed a favorable bioavailability of 75.2%. As demonstrated by the in vitro and in vivo experiments, no reported toxic metabolites were found and the risk of potential liver toxicity was low.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 4","pages":"929 - 943"},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622132","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":"Correction: Anticancer therapeutic potential of silibinin: current trends, scope and relevance","authors":"Anupam Sharma,&nbsp;Sunil Kumar,&nbsp;Virender Pahil,&nbsp;Babli Mamoria,&nbsp;Mukesh Yadav,&nbsp;Nirmala Sehrawat,&nbsp;Manoj Singh,&nbsp;Anil Kumar Sharma","doi":"10.1007/s00044-025-03388-3","DOIUrl":"10.1007/s00044-025-03388-3","url":null,"abstract":"","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 4","pages":"825 - 826"},"PeriodicalIF":2.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622273","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, biological evaluation, and in silico studies of imidazo[2,1-b][1,3,4]thiadiazole derivatives as cholinesterase inhibitors","authors":"Wen-Rong Du,&nbsp;Yi-Xuan Wang,&nbsp;Xue-Wei Zhou,&nbsp;Yong Lan,&nbsp;Ben-Ben Wei,&nbsp;Xin-Yuan Guo,&nbsp;Xiao-Ke Wang,&nbsp;Zheng-Yue Ma","doi":"10.1007/s00044-025-03387-4","DOIUrl":"10.1007/s00044-025-03387-4","url":null,"abstract":"<div><p>In this study, a series of imidazo[2,1-<i>b</i>][1,3,4]thiadiazole derivatives were designed, synthesized, and evaluated as potential cholinesterase inhibitors (ChEIs) for the treatment of Alzheimer’s disease (AD). Furthermore, the antioxidant activities of these compounds were examined by the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay. The inhibition assay against cholinesterase (ChE) revealed that these synthesized compounds exhibited moderate inhibitory activities against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Notably, some of the tested compounds had varying antioxidant activities. Specifically, compound <b>20aa</b> (eeAChE, IC₅₀ = 0.75 μM; eqBChE, IC₅₀ = 4.11 μM; SI = 5.48) was found to be the most effective ChEI, exhibiting approximately 5-fold greater activity against AChE and 4-fold greater activity against BChE compared to galantamine. Additionally, compound <b>20aa</b> also possessed antioxidant activity, with IC₅₀ value of 442.87 µM. To understand the binding mode of compound <b>20aa</b>, molecular docking studies were performed, and the results indicated that compound <b>20aa</b> could interact with amino acid residues in the catalytic active site (CAS) of both BChE and AChE, as well as with the peripheral anionic site (PAS) of AChE. Among them, compound <b>20aa</b> showed a mixed inhibition pattern with AChE, which aligned with the results of the enzyme kinetics studies. Molecular dynamics (MD) simulation studies demonstrated the stability of the <b>20aa</b>-AChE/BChE complexes. Considering its biological activity and molecular properties, compound <b>20aa</b> could be a promising lead compound for the development of AD drugs.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 4","pages":"910 - 928"},"PeriodicalIF":2.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622263","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":"An evaluation of spirooxindoles as blocking agents of SARS-CoV-2 spike/ACE2 interaction: synthesis, biological evaluation and computational analysis","authors":"Albert Enama Ehinak,&nbsp;Maloba M. M. Lobe,&nbsp;Donatus B. Eni,&nbsp;Conrad V. Simoben,&nbsp;Ian Tietjen,&nbsp;Mathieu J. Mbenga Tjegbe,&nbsp;Joel Cassel,&nbsp;Joseph M. Salvino,&nbsp;Luis J. Montaner,&nbsp;Wolfgang Sippl,&nbsp;Simon M. N. Efange,&nbsp;Fidele Ntie-Kang","doi":"10.1007/s00044-025-03386-5","DOIUrl":"10.1007/s00044-025-03386-5","url":null,"abstract":"<div><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has gained significant public health attention owing to its devastating effects on lives and livelihoods worldwide. Due to difficult access to vaccines in many developing countries and the inefficiency of vaccines in providing complete protection even with fully vaccinated persons, there remains the need for the development of novel drugs to combat the disease. This study describes the in vitro activity of a library of fifty-five spiro-fused tetrahydroisoquinoline–oxindole hybrids (spirooxindoles) as potential blocking agents of the interaction between the SARS-CoV-2 viral spike and the human angiotensin-converting enzyme 2 (ACE2) receptor, essential for viral transmission. The synthesis was conducted by the Pictet-Spengler condensation of phenethylamine and isatin derivatives, while the screening against spike-ACE2 interaction was done using our previously described AlphaScreen fluorescent assay. The in vitro screening identified compound (<b>11j</b>) as the most active, showing a 50% inhibitory concentration (IC₅₀) of 3.6 μM against SARS-CoV-2 spike/ACE2 interaction. Structure-activity relationships explained via molecular docking studies and the computation of binding free energy of each compound with respect to the spike/ACE2 protein-protein interaction showed that the most active compound possesses a bulky naphthyl group, which addresses voluminous hydrophobic regions of the ACE2 binding site and interacts with the hydrophobic residues of the target. Therefore, these compounds could be potentially useful in searching for SARS-CoV-2 spike/ACE2 interaction blocking agents.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 4","pages":"895 - 909"},"PeriodicalIF":2.6,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-025-03386-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621949","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}

{"title":"Exploring the potential of isatin hybrids as anticancer agents: recent advances and future prospective","authors":"Parveen Gahlyan,&nbsp;Tanisha Chauhan,&nbsp;Priyanka Jhajharia,&nbsp;Balaram Pani,&nbsp;Rakesh Kumar","doi":"10.1007/s00044-025-03385-6","DOIUrl":"10.1007/s00044-025-03385-6","url":null,"abstract":"<div><p>Synthesis of hybrid molecules via molecular hybridization technique has been known to be a promising strategy which involves the blending of two pharmacophoric groups joined via covalent bonds to make a single entity that can serve as chemotherapeutic agents. “Isatin” is an important toolbox for medicinal chemists with high pharmacological profile being known as the “privileged scaffold” in the field of drug development. Various drugs consisting of isatin core have been shown to have pronounced therapeutic effects on several cancers as they have prophylactic role towards free radicals that cause cancer. This report highlights the most recent advances from the past four years in the development of isatin based drugs against several human cancer cell lines such as MCF-7 (breast cancer cell line), A-549 (lung cancer cell line), Hep-G2 (liver cancer cell line) and some other cell lines, respectively.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 4","pages":"827 - 848"},"PeriodicalIF":2.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622100","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":"A mild and catalyst-free α-benzoyloxylation of tertiary amides","authors":"Md Imdadul H. Khan,&nbsp;Jiaxin Yang,&nbsp;Seong Jong Kim,&nbsp;Hoang V. Le","doi":"10.1007/s00044-025-03381-w","DOIUrl":"10.1007/s00044-025-03381-w","url":null,"abstract":"<div><p>An α-C–H oxygenation of amides using Togni reagent II and an umpolung strategy is reported. α-Benzoyloxy amides were prepared in moderate-to-high yields from tertiary amides under mild and catalyst-free reaction conditions. All reagents are commercially available, easy to use, and compatible with various functional groups and rings. α-Benzoyloxy amides could be easily transformed into the corresponding α-hydroxy amides in almost quantitative yields. This transformation has significant potential for the synthesis of important compounds in pharmaceutical and agricultural fields.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 4","pages":"849 - 854"},"PeriodicalIF":2.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622189","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":"Novel conjugated 5-alkenyl rhodanine tethered 1,4-benzodioxane derivatives as dual-chitinases inhibitors to hinder the growth of Asian corn borer","authors":"Jinxiu Chen,&nbsp;Dongmei Shi,&nbsp;Zhiyang Jiang,&nbsp;Renxuan Zou,&nbsp;Jingyu Zhang,&nbsp;Qing Han,&nbsp;Na Wang,&nbsp;Zhijian Xu,&nbsp;Qing Yang,&nbsp;Hongxia Duan","doi":"10.1007/s00044-025-03382-9","DOIUrl":"10.1007/s00044-025-03382-9","url":null,"abstract":"<div><p><i>Of</i>ChtI and <i>Of</i>Chi-h are ideal targets for developing agricultural inhibitors against <i>Ostrinia furnacalis</i>. In order to further confirm the importance of conjugated systems in rhodanine derivatives, sixteen novel 1,4-benzodioxane-tethered-rhodanine derivatives were designed and synthesized with or without C=C double bond of 5-alkenyl rhodanine skeleton. Among them, compounds <b>3a</b>–<b>3h</b>, with preserved 5-alkenyl rhodanine skeleton, all exhibited much better inhibitory activities against both <i>Of</i>ChtI and <i>Of</i>Chi-h, compared to that of the corresponding reduced compounds <b>4a</b>–<b>4h</b> without its C=C double bond. The inhibitory mechanism demonstrated that the 5-alkenyl rhodanine conjugated plane was conducive to improving the binding affinity with both two chitinases. Compound <b>3g</b> was identified as the most potential dual-chitinases inhibitor against <i>Of</i>ChtI (<i>K</i>_i = 2.57 μM) and <i>Of</i>Chi-h (<i>K</i>_i = 2.03 μM). The bioassay study also indicated that compound <b>3g</b> displayed the best insecticidal activity against <i>O. furnacalis</i> and distinctive sublethal effect in regulating its growth and development. These 1,4-benzodioxane-tethered-rhodanine derivatives deserved further investigation as novel dual-chitinases inhibitor candidates in the control of <i>O. furnacalis</i>.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 4","pages":"882 - 894"},"PeriodicalIF":2.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622190","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 and evaluation of tetrahydrobenzo[cd]indole derivatives as glycogen phosphorylase inhibitors","authors":"Panarat Arunrattiyakorn,&nbsp;Chanitha Juiprasert,&nbsp;Symeon M. Koulas,&nbsp;Pornthip Boonsri,&nbsp;Thammarat Aree,&nbsp;Maho Yagi-Utsumi,&nbsp;Koichi Kato,&nbsp;Demetres D. Leonidas","doi":"10.1007/s00044-025-03384-7","DOIUrl":"10.1007/s00044-025-03384-7","url":null,"abstract":"<div><p>A series of tetrahydrobenzo[<i>cd</i>]indole derivatives was synthesized by condensation of a fungal metabolite hyphodermin A, a naphtho[1,2-<i>c</i>]furan-3,9-dione derivative, and various anilines in methanol. Using this approach, ten analogs (<b>3a</b>–<b>3j</b>) were synthesized and tested as inhibitors against glycogen phosphorylase (GP). While compounds <b>3e</b> and <b>3i</b> bearing hydrophobic bromo and trifluoromethyl groups showed moderated inhibition (<i>K</i>_i = 32.3–57.4 μΜ), compound <b>3g</b> with hydroxy group had the most potent activity with a <i>K</i>_i value of 7.9 ± 0.7 μΜ against human liver GPa. An X-ray crystallography study of the rabbit muscle GPb-<b>3g</b> complexes revealed that this inhibitor binds at a subsite within the indole binding site of GP which has not been previously observed to bind ligands.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 4","pages":"870 - 881"},"PeriodicalIF":2.6,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622156","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":"Anticancer therapeutic potential of silibinin: current trends, scope and relevance","authors":"Anupam Sharma,&nbsp;Sunil Kumar,&nbsp;Virender Pahil,&nbsp;Babli Mamoria,&nbsp;Mukesh Yadav,&nbsp;Nirmala Sehrawat,&nbsp;Manoj Singh,&nbsp;Anil Kumar Sharma","doi":"10.1007/s00044-025-03383-8","DOIUrl":"10.1007/s00044-025-03383-8","url":null,"abstract":"<div><p>The use of natural plants as powerful sources for the treatment of chronic illnesses has drawn more attention from researchers to herbal remedies. Silybum marianum, a naturally occurring plant, is the source of silymarin, a flavonolignan which is used to guard against a range of illnesses in both clinical and experimental contexts. Silymarin is easily absorbed and metabolised in phases I and II, according to its pharmacokinetics. Phase II is the site of its conjugation, and it is finally excreted in bile and urine. In a variety of tissues, the primary active components, silymarin and silibinin, provide protection against cancer. Silibinin has been shown to have anti-inflammatory, anti-angiogenic, antioxidant, and anti-metastatic properties. This further helps to block many oncogenic pathways from being activated such as NF-κB, Wnt/β-catenin, PI3K/Akt, and MAPK pathways. Hence, silibinin helps in preventing proliferation of the tumor cells, initiating the cell cycle arrest, and induce cancer cells to die. This review gives the thorough analysis of silibinin in distinct types of cancer such as lung, liver, breast, bladder, prostate, skin and ovarian cancer.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 4","pages":"809 - 824"},"PeriodicalIF":2.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622058","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}