Medicinal Chemistry Research最新文献

{"title":"Designations of new biological drugs","authors":"Sarah K. Branch, Israel Agranat","doi":"10.1007/s00044-025-03470-w","DOIUrl":"10.1007/s00044-025-03470-w","url":null,"abstract":"","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 10","pages":"2003 - 2007"},"PeriodicalIF":3.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184092","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: Synthesis and inhibitory activity against enzymes responsible for Type 2 diabetes mellitus of lactose-conjugated thiosemicarbazones from substituted acetophenones","authors":"Hoang Thi Kim Van, Nguyen Dinh Thanh, Duong Thu Nguyet","doi":"10.1007/s00044-025-03474-6","DOIUrl":"10.1007/s00044-025-03474-6","url":null,"abstract":"","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 10","pages":"2195 - 2195"},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184185","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 comprehensive review of the phytochemical and pharmacological potential of Alnus glutinosa (L.) Gaertn., (Black Alder)","authors":"Atif Ali Khan Khalil,&nbsp; Salsabila,&nbsp;Hanhong Bae","doi":"10.1007/s00044-025-03473-7","DOIUrl":"10.1007/s00044-025-03473-7","url":null,"abstract":"<div><p><i>Alnus glutinosa</i> (Betulaceae), commonly known as black alder, is a traditional medicinal tree with ecological, ethnobotanical, and pharmacological importance. This review presents the first comprehensive assessment of its medicinal potential, integrating botanical background, phytochemistry, and bioactivities. Scientific investigations have validated the traditional applications and revealed diverse pharmacological properties, including anticancer, antioxidant, antibacterial, antifungal, anti-inflammatory, hepatoprotective, and wound-healing effects. These effects can be attributed, in large part, to bioactive chemical compounds such as diarylheptanoids, flavonoids, phenolics, tannins, terpenoids, and steroids. These constituents modulate oxidative stress, inflammatory pathways, and other important cellular functions. This work highlights the therapeutic value of <i>A. glutinosa</i> and exposes crucial gaps in knowledge by combining chemical composition with pharmacological insights. Specifically, the work focuses on the relationship between the two. In particular, additional mechanistic investigations and clinical validation are required in order to advance its function in contemporary medical practice. Overall, the review provides a foundation for future studies on <i>A. glutinosa</i>, supporting its potential as a promising source of bioactive compounds for drug development.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 10","pages":"2052 - 2074"},"PeriodicalIF":3.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184090","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 cholinesterase inhibitors based on the 2-aminothiazole scaffold","authors":"Wen-Rong Du,&nbsp;Xue-Wei Zhou,&nbsp;Yi-Xuan Wang,&nbsp;Zheng-Yue Ma","doi":"10.1007/s00044-025-03468-4","DOIUrl":"10.1007/s00044-025-03468-4","url":null,"abstract":"<div><p>In this study, a series of 2-aminothiazole derivatives were designed, synthesized, and evaluated as potential cholinesterase inhibitors (ChEIs) for the treatment of Alzheimer’s disease (AD). Subsequently, the antioxidant activities of these synthesized compounds were assessed using the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay. The results of the cholinesterase (ChE) inhibition assays revealed that most of the compounds exhibited certain inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among them, compound <b>14s</b> demonstrated the most potent inhibitory activity against AChE, with IC₅₀ value of 3.54 μM. Meanwhile, compound <b>14s</b> also exhibited moderate inhibitory activity against BuChE, with IC₅₀ value of 7.95 μM. The inhibitory activities of compound <b>14s</b> against both AChE and BuChE were superior to those of galantamine (AChE: IC₅₀ = 3.47 μM; BuChE: IC₅₀ = 17.31 μM). The type of inhibition for compound <b>14s</b> was determined through enzyme kinetic studies, and the results showed that the compound was a mixed type inhibitor. In addition, molecular docking results showed that compound <b>14s</b> could interact with the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE, which was consistent with the enzyme kinetic experimental results. Molecular dynamics (MD) simulation studies demonstrated the stability of the <b>14s</b>-AChE/BuChE complexes. Moreover, results from the DPPH free radical scavenging assay indicated that the compounds also exhibited antioxidant activity. Collectively, these experimental results indicated that the designed and synthesized ChEI <b>14s</b> exhibits potential for further research.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 10","pages":"2162 - 2178"},"PeriodicalIF":3.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184157","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 biological evaluation of triazole alcohols containing an indole-3-methyl(phenyl)amino side chain against fluconazole-resistant Candida albicans","authors":"Zefei Fan,&nbsp;Lijiao Yang,&nbsp;Jidong Wang,&nbsp;Yafei Hou,&nbsp;Fei Zou,&nbsp;Tianyu Zhang,&nbsp;Yongyan Fu,&nbsp;Yue Zhang,&nbsp;Ruirui Wang,&nbsp;Shichong Yu,&nbsp;Guanghui Ni","doi":"10.1007/s00044-025-03469-3","DOIUrl":"10.1007/s00044-025-03469-3","url":null,"abstract":"<div><p>A novel series of triazole alcohols containing an indole-3-methyl(phenyl)a- mino side chain have been synthesized as derivatives of fluconazole. The title compounds were synthesized via the ring-open reaction of epoxide with various N-aryl indole-3-methylamine. Compound <b>C04</b> exhibited significant inhibitory activity against fluconazole-resistant <i>Candida albicans</i> (ATCC-14053) with an MIC₅₀ of 2.31 μM. Notably, compound <b>C08</b> displayed potent inhibition against seven fungal pathogens including two clinically isolated fluconazole-resistant strains. The time-kill assays demonstrated that compounds C04 and C08 exhibited significant growth inhibitory effects against <i>Candida albicans</i> ATCC 14053. Further studies confirmed their potent inhibitory activity against <i>C. albicans</i> biofilm development. Cytotoxicity evaluation demonstrated that both compounds exhibited favorable safety profiles. These results indicate that <b>C04</b> and <b>C08</b> are promising antifungal drug candidates, providing novel therapeutic strategies to combat clinically resistant fungal infections.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 10","pages":"2179 - 2194"},"PeriodicalIF":3.1,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-025-03469-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184184","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":"Plant-derived pyroptosis inducers as a therapeutic strategy in drug-resistant cancers","authors":"Kang Zi Khor,&nbsp;Adam Azlan,&nbsp;Nozlena Abdul Samad,&nbsp;Emmanuel Jairaj Moses,&nbsp;George George Mathew,&nbsp;Julia Joseph","doi":"10.1007/s00044-025-03472-8","DOIUrl":"10.1007/s00044-025-03472-8","url":null,"abstract":"<div><p>Drug resistance in cancer therapy, often due to the evasion of apoptosis, highlights the need for alternative treatments. Pyroptosis is a type of inflammatory programmed cell death mediated by gasdermin proteins. It offers a promising approach as it can trigger anti-tumour immunity through cytokine release. Plant-derived compounds, rich in bioactive metabolites, can induce pyroptosis via inflammasome activation, gasdermin cleavage and reactive oxygen species (ROS) generation. Phytochemicals like curcumin, quercetin, cucurbitacin B and kaempferol selectively target cancer cells while modulating inflammation in healthy tissues. Combining these compounds with chemotherapy, immunotherapy or nanoparticle-based delivery systems enhance their therapeutic efficacy and overcome drug resistance. Despite promising preclinical findings, clinical translation remains challenging, necessitating further research to optimise safety, specificity, and delivery mechanisms. This review consolidates current knowledge on plant-derived pyroptosis inducers, highlighting their mechanisms, therapeutic potential, and future directions in combating drug-resistant cancers.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 10","pages":"2137 - 2146"},"PeriodicalIF":3.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-025-03472-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184091","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":"Silibinin: a natural flavonoid with multifaceted anticancer potential and therapeutic challenges","authors":"Snigdha Singh,&nbsp;Arpit Sharma,&nbsp;Tanu Pandey,&nbsp;Shivani Gupta,&nbsp;Alok Shukla,&nbsp;Santosh Kumar Singh,&nbsp;Amit Singh","doi":"10.1007/s00044-025-03466-6","DOIUrl":"10.1007/s00044-025-03466-6","url":null,"abstract":"<div><p>Silibinin, the principal bioactive flavonolignan of <i>Silybum marianum</i> (milk thistle), has emerged as a promising natural agent with multifaceted anticancer potential. Extensive preclinical studies demonstrate its diverse pharmacological properties, including antioxidant, anti-inflammatory, and chemopreventive activities, which collectively contribute to its antitumor effects. At the molecular level, silibinin exerts cytotoxicity through the induction of apoptosis, involving both extrinsic (death receptor-mediated) and intrinsic (mitochondria-dependent) pathways. It modulates key signaling cascades such as EGFR, STAT3, and PI3K/AKT/mTOR, leading to suppression of proliferation, angiogenesis, invasion, and modulation of autophagy, stemness and Senescence. Importantly, silibinin acts as a modulator of apoptosis by restoring the balance between pro- and anti-apoptotic proteins, thereby sensitizing cancer cells to programmed cell death. Evidence across multiple malignancies, including hepatocellular carcinoma, breast, lung, and colorectal cancers etc, highlights its broad-spectrum therapeutic relevance. Clinical studies, though limited, suggest that silibinin may enhance the efficacy of standard chemotherapeutic, radiotherapeutic, and targeted regimens while reducing associated toxicities, underscoring its role as a synergistic adjuvant. However, challenges such as poor bioavailability, variable pharmacokinetics, and limited large-scale clinical validation constrain its translational application. To address these limitations, novel strategies such as nanocarrier-based delivery, structural modifications, and combination therapies are being actively investigated. Overall, silibinin represents a compelling natural flavonoid with dual preventive and therapeutic roles in oncology, though future research must overcome pharmacological barriers to fully harness its clinical potential.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 10","pages":"2115 - 2136"},"PeriodicalIF":3.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184187","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 in vitro antitrypanosomatid efficacy of 5-benzylidene-2-thiohydantoin esters","authors":"Simon S. Mnyakeni-Moleele,&nbsp;Janine Aucamp,&nbsp;Helena D. Janse van Rensburg,&nbsp;Keisuke Suganuma,&nbsp;David D. N’Da","doi":"10.1007/s00044-025-03463-9","DOIUrl":"10.1007/s00044-025-03463-9","url":null,"abstract":"<div><p>Neglected tropical diseases caused by protozoan parasites such as <i>Leishmania</i> (<i>L</i>.) and <i>Trypanosoma</i> (<i>T</i>.) species pose significant health, social, and economic challenges globally. Current treatments are often toxic, with complex administration routes. Additionally, these drugs are prone to parasite resistance, necessitating the search for novel therapeutic agents. To this end, we initiated a program to investigate the antiparasitic potential of arylidene compounds. In this preliminary study, a small series of 5-benzylidene-2-thiohydantoin esters was synthesised in a multi-step process and evaluated for antitrypanosomatid activity against <i>Leishmania</i> and <i>Trypanosoma</i> species. The in vitro biological evaluation revealed promising leishmanicidal activity against the antimony-resistant <i>L. donovani</i> strain 9515 and <i>L. major</i> strain NIH S, as well as trypanocidal activity against the <i>T. congolense</i> strain IL3000. Most compounds exhibited low cytotoxicity toward mammalian cells, resulting in high selectivity indices. Several early leads against visceral and cutaneous leishmaniasis, with similar potency to the reference drug amphotericin B, were identified (IC₅₀ &lt; 1 µM, SI &gt; 100). For example, <b>A1-13</b> demonstrated cidal activity in the nanomolar range against intracellular amastigotes of <i>L. donovani</i> (IC₅₀ 0.41 µM, SI 244) and <b>A2-4</b> against <i>L. major</i> (IC₅₀ 0.49 µM, SI 204). Additionally, <b>A2-5</b> (IC₅₀ 0.35 µM, SI 452) was identified as an early lead against animal-infective <i>T. congolense</i> trypomastigotes, a causative agent of the cattle wasting disease nagana. Drug-likeness predictions confirmed favourable physicochemical properties with minimal predicted toxicity risks. These findings provide valuable insights into the development of thiohydantoin-based therapeutics for neglected tropical diseases; however, the mechanism of action and in vivo antitrypanosomatid efficacy of the promising early leads should be further determined.</p></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 10","pages":"2147 - 2161"},"PeriodicalIF":3.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-025-03463-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184190","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":"Comparative analysis on artificial intelligence methods for DTI and DTBA prediction in drug repurposing","authors":"Sheo Kumar,&nbsp;Amritpal Singh","doi":"10.1007/s00044-025-03465-7","DOIUrl":"10.1007/s00044-025-03465-7","url":null,"abstract":"<div><p>Drug repurposing has evolved as an attractive approach in the search for new therapeutic applications that are shorter in development time and lower in cost. At the core of drug repurposing, the key challenge in this field is the accurate prediction of drug-target interactions (DTIs) and drug-target binding affinities (DTBAs). Various Artificial Intelligence (AI) techniques, including machine learning (ML) and deep learning (DL) methods, have proven to be significant in improving the prediction capability of the DTI and DTBA models. In this review, we provide critical insights into the current state-of-the-art AI methods used for the prediction of DTI and DTBA by highlighting major progress, bottlenecks, and potential future research directions. Classify these approaches according to their algorithmic framework, feature extraction methods, data source, and performance measures, and provide an extensive review of their strengths against limitations. Lastly, the limitations of current AI-assisted DTI and DTBA prediction methods in drug repurposing applications are summarized and highlight possible directions to address those challenges.</p></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 10","pages":"2086 - 2114"},"PeriodicalIF":3.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184089","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 updated review on phytochemical and pharmacological potential of Portulaca oleracea L.","authors":"Azazahemad A. Kureshi,&nbsp;Sharad Kumar Tripathi,&nbsp;Premlata Kumari","doi":"10.1007/s00044-025-03467-5","DOIUrl":"10.1007/s00044-025-03467-5","url":null,"abstract":"<div><p><i>Portulaca oleracea L</i>., commonly known as purslane or pigweed, is a fleshy, drought-resistant weed belonging to the family Portulacaceae. It grows worldwide, including regions such as Asia, Europe, China, the Mediterranean, Japan, the U.S., Africa, and Australia<i>. P. oleracea</i> leaves have long been used in traditional cuisine, eaten as a steamed green, added to pickles, tossed in salads, or used to thicken soups. Rich in essential nutrients, this plant is especially valued for its abundant omega-3 fatty acids, which play a vital role in growth, development, and protection against diseases. It also contains diverse bioactive compounds, including flavonoids, carotenoids, monoterpene glycosides, phenolic glycosides, triterpenoids, alkaloids, carbohydrates, proteins, vitamins, minerals, and electrolytes. These bioactive compounds give <i>P. oleracea</i> its diverse medicinal benefits, including antioxidant, heart protective, anti-atherosclerotic, anti-inflammatory, cholesterol-lowering, blood-thinning, glucose regulating and antimicrobial effects. Recent research has also explored using <i>P. oleracea</i> extracts to produce biogenic metallic nanoparticles, opening new possibilities in photocatalysis and advanced medical nanotechnology. This review comprehensively summarizes the updated phytochemical profile and pharmacological activities of purslane extracts, linking traditional knowledge with cutting-edge applications with emphasizing its role as a vital resource for human health.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 10","pages":"2008 - 2051"},"PeriodicalIF":3.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184188","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}