European Journal of Medicinal Chemistry Reports最新文献

{"title":"Design, synthesis, characterization and antidiabetic evaluation of 3,5-substituted thiazolidinediones: Evidenced by network pharmacology, Molecular docking, dynamic simulation, in vitro and in vivo assessment","authors":"Shankar Gharge,&nbsp;Shankar G. Alegaon,&nbsp;Swaroop Jadhav,&nbsp;Shriram D. Ranade,&nbsp;Rohini S. Kavalapure","doi":"10.1016/j.ejmcr.2024.100213","DOIUrl":"10.1016/j.ejmcr.2024.100213","url":null,"abstract":"<div><p>In search of new antidiabetic agents, heterocyclic compounds containing 3,5-Substituted thiazolidinedione moieties were synthesized through a concise three-step reaction process. The synthesis involved Knoevenagel condensation at the 5th position of the 3,5-Substituted thiazolidinedione ring-system (6a-6c). Comprehensive physicochemical and spectral analyses, including FTIR, HR-MS, ¹H NMR and ¹³C NMR, were performed to characterize the synthesized compounds. The synthesized derivatives were subjected to evaluation for their <em>In vivo</em> anti-diabetic activity against diabetes induced wistar rats and <em>In vitro</em> activity against <em>α-amylase, α-glucosidase</em> and glucose uptake by yeast cells. On the basis of the combined results of network pharmacology<em>, In vitro</em> and animal study experiments revealed that the compounds 6c predicted to have the greatest effect out of the compounds (6a-6c), showing interactions with targets exhibited potential binding patterns against the active site of target <em>α-amylase, α-glucosidase</em> with modulating <em>AMY2A, GAA, PPARG, PIK3CA, PRKCB, INSR,</em> and <em>PRKCB</em> signalling pathways and this is evidenced by molecular docking, dynamics simulation (MD) studies. Further, compound 6c showed <em>In vitro α-amylase, α-glucosidase</em> inhibitory activity with IC₅₀ value of 86.06 ± 1.1 μM and 74.97 ± 1.23 μM as opposed to standard acarbose (IC₅₀ value of 26.89 ± 3.12 and 29.25 ± 0.15 μM) and 58.23 ± 0.13 % of glucose uptake and also exhibited significant reduction (p &lt; 0.001) in blood glucose levels (114 ± 1.17 mg/dL) comparable to the effect of pioglitazone (102.2 ± 0.79 mg/dL). The present study suggests that modified thiazolidinediones act as potential lead compounds to carter the need of antidiabetic agents.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100213"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000852/pdfft?md5=6937eab5d75386afd4b218c9aad7de7a&pid=1-s2.0-S2772417424000852-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142167391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and efficacy study of an ALK inhibitor AMX6001 in anaplastic large cell lymphoma Karpas299 mice models","authors":"Debasis Das,&nbsp;Lingzhi Xie,&nbsp;Dandan Qiao,&nbsp;Yuxi Cao,&nbsp;Jianhe Jia,&nbsp;Yong Li,&nbsp;Jian Hong","doi":"10.1016/j.ejmcr.2024.100209","DOIUrl":"10.1016/j.ejmcr.2024.100209","url":null,"abstract":"<div><p>Anaplastic lymphoma kinase (ALK) is an attractive therapeutic target for the treatment of anaplastic large cell lymphoma (ALCL). We identified novel deuterated 2,4-diarylamino pyrimidine compounds as potent ALK inhibitors. The compound <strong>9</strong> (<strong>AMX6001</strong>) showed better <em>in vitro</em> activity against ALK and NPM-ALK kinase and significantly inhibited proliferation of Karpas299 and SU-DHL-1 cell lines. <em>In vivo</em> efficacy of compound <strong>9</strong> was better than reference standard ceritinib in ALCL Karpas299 mice models. Daily oral treatment of compound <strong>9</strong> (25 mg/kg) induced tumor suppression TGI up to 95.8 % in ALCL models.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100209"},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000815/pdfft?md5=a3a86c8978cc4e8877ca8b225053a789&pid=1-s2.0-S2772417424000815-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142151803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metal complexes of saccharin and thiosaccharin as potential anticancer and antimicrobial agents","authors":"Ceyda Icsel ,&nbsp;Veysel T. Yilmaz ,&nbsp;Okan Z. Yesilel ,&nbsp;William T.A. Harrison","doi":"10.1016/j.ejmcr.2024.100205","DOIUrl":"10.1016/j.ejmcr.2024.100205","url":null,"abstract":"<div><p>Based on the chemotherapeutic success of cisplatin, carboplatin and oxaliplatin as anticancer drugs, and silver sulfadiazine (AgSDZ) as an antibacterial drug, exploration of the anticancer and antibacterial potential of new metal complexes has received increasing attention during the last three decades. Saccharin (sacH) is a well-known worldwide artificial sweetener. Its deprotonated form (sac) is a polyfunctional ligand, coordinating to different metals due to the presence of hard and soft donor sites (see comment below). In the last two decades, a large number of mixed-ligand metal complexes containing sac and tsac ligands have been synthesized and in some cases, they have demonstrated better <em>in vitro</em> and <em>in vivo</em> biological activities than approved standard drugs. This review describes the design, anticancer and antimicrobial activity screening of metal complexes of sac and its thio derivative (tsac) as prospective drug candidates. The metal sac complexes herein are categorized according to the ancillary ligands present in the complexes, and their anticancer and antimicrobial activities are discussed in detail. The main molecular targets and cellular pathways involved in the mechanism of action of the metal complexes were also explored. The growing field demonstrates promising <em>in vitro</em> and <em>in vivo</em> results with a significant interest for future research in medicinal inorganic chemistry.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100205"},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000773/pdfft?md5=49e2a34d02c60c755a37c3ac401e827b&pid=1-s2.0-S2772417424000773-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142058061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current trends in silica based drug delivery systems","authors":"Rozhan Khoz ,&nbsp;Fateme Yazdian ,&nbsp;Mehrab Pourmadadi ,&nbsp;Abbas Rahdar ,&nbsp;Sonia Fathi-karkan ,&nbsp;Sadanand Pandey","doi":"10.1016/j.ejmcr.2024.100206","DOIUrl":"10.1016/j.ejmcr.2024.100206","url":null,"abstract":"<div><p>Traditional drug delivery systems have fallen short in addressing the complex medical and therapeutic needs of patients, necessitating the development of more efficient alternatives. These novel systems aim to enhance treatment efficacy while minimizing adverse effects. Advances in drug delivery technology have significantly improved drug loading and release, administration methods, pharmacological profiles, and the creation of innovative drug formulations. This review delves into current methodologies employed in silica-based targeted drug delivery systems. After examining the structure and properties of various silicas, we focus on mesoporous nanoparticles for targeted drug delivery, exploring existing approaches and addressing critical concerns such as silica safety and biodegradability. Additionally, this review provides a brief overview of bioassays, cell tracking, and tumor-specific targeting strategies.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100206"},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000785/pdfft?md5=3426e03014d8ae36be2b9ada6b4f533b&pid=1-s2.0-S2772417424000785-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142099079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of pyrazole and pyrazoline derivatives of β-ionone: Exploring anti-inflammatory potential, cytotoxicity, and molecular docking insights","authors":"Monika Sihag ,&nbsp;Anju Manuja ,&nbsp;Swati Rani ,&nbsp;Rinku Soni ,&nbsp;Neha Rani ,&nbsp;Sandeep Malik ,&nbsp;Kirti Bhardwaj ,&nbsp;Balvinder Kumar ,&nbsp;Mayank Kinger ,&nbsp;Monika Miglani ,&nbsp;Deepak Kumar Aneja","doi":"10.1016/j.ejmcr.2024.100204","DOIUrl":"10.1016/j.ejmcr.2024.100204","url":null,"abstract":"<div><p>In the present paper, pyrazole and pyrazoline derivatives of β-ionone were synthesized. The protocol involved intramolecular oxidative C–H amination of hydrazone to yield corresponding pyrazole in moderate to good yields. Another methodology comprising of condensation of hydrazine hydrochloride with β-ionone in methanol leading to pyrazoline and its oxidative dehydrogenation using hypervalent iodine reagent to synthesize pyrazole is also achieved. One pot methodology for synthesis of pyrazole is also developed by refluxing the hydrazine hydrochloride with β-ionone in acetic acid. The structures of the synthesized compounds were elucidated using ¹H NMR, ¹³C NMR, FTIR and mass spectrometry. All the pyrazole and pyrazoline derivatives were subjected to bovine serum albumin assay for <em>in-vitro</em> anti-inflammatory activity and all the compounds exhibited good to excellent activity. Compounds containing bromo and sulfonamide group exhibited inhibition rates of 87.36 % and 85.82 %, respectively, at a concentration of 0.5 mg/mL, surpassing the efficacy of the standard drug celecoxib (81.67 %). Further, cytotoxicity of the compounds was also evaluated against VERO cell line and all the compounds exhibited the cytotoxic values almost similar to the standard. Molecular docking was performed to study binding affinity of the potent compounds i. e bromo bearing pyrazole and sulfonamide bearing pyrazoline into the crystal structure of COX-II enzyme (PDB ID: <span><span>3LN1</span><svg><path></path></svg></span>) at celecoxib binding site to determine the binding energy and interactions.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100204"},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000761/pdfft?md5=1f6fff0a331bc86608e264d463bc5212&pid=1-s2.0-S2772417424000761-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142058065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, molecular dynamics studies and biological evaluations of 4-hydroxy-5-pyrrolinone-3-carbohydrazides as HIV-1 integrase inhibitors","authors":"Nafiseh Karimi ,&nbsp;Amirreza Dowlati Beirami ,&nbsp;Rouhollah Vahabpour Roudsari ,&nbsp;Zahra Hajimahdi ,&nbsp;Afshin Zarghi","doi":"10.1016/j.ejmcr.2024.100208","DOIUrl":"10.1016/j.ejmcr.2024.100208","url":null,"abstract":"<div><p>Acquired immune deficiency syndrome (AIDS) diseases despite the efficacy of anti-HIV therapy, remain one of the human's most serious problems. Hence, the introduction of novel anti-HIV agents as first-line therapy is still required. HIV integrase lacking human enzyme homologous is an interesting target for developing new anti-HIV drugs. Following our attempts to describe active integrase inhibitor structures, here a series of novel 4-Hydroxy-5-pyrrolinone-3-carbohydrazides as HIV integrase inhibitor agents were identified. Biological results showed that all compounds could inhibit integrase strand transfer reaction and also exhibited anti-HIV activity in a cell-based assay. The interaction between integrase and designed compounds was investigated using molecular docking and molecular dynamics simulations.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100208"},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000803/pdfft?md5=e9b5e1971d09654fd918e70450d89bc0&pid=1-s2.0-S2772417424000803-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142039843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, α-glucosidase inhibition and hypoglycemic activity of 3-aceto(benzo)hydrazide-1,2,4-triazines as potential anti-diabetic agents","authors":"Mehdi Valipour ,&nbsp;Zahra Zakeri Khatir ,&nbsp;Kaveh Kiadaliry ,&nbsp;Somayeh Mojtabavi ,&nbsp;Mohammad Ali Faramarzi ,&nbsp;Mohammad Shokati Sayyad ,&nbsp;Mohammad Seyedabadi ,&nbsp;Majid Ghasemian ,&nbsp;Seyedeh Mahdieh Hashemi ,&nbsp;Hamid Irannejad","doi":"10.1016/j.ejmcr.2024.100207","DOIUrl":"10.1016/j.ejmcr.2024.100207","url":null,"abstract":"<div><p>Type 2 diabetes is a common condition that causes the level of glucose in the blood to become too high and α-glucosidase inhibitors are therapeutic agents in managing type 2 diabetes. I<em>n</em> the present study, we report a new series of 3-aceto(benzo)hydrazide-1,2,4-triazine analogs as potential therapeutic agents against type 2 diabetes. In the <em>in vitro</em> evaluations, most compounds showed much stronger α-glucosidase inhibitory activity than the standard drug acarbose. Especially, compound <strong>2A</strong>, (N'-(5,6-diphenyl-1,2,4-triazin-3-yl)-4-methoxybenzohydrazide) as the most active compound showed IC₅₀ = 12.0 μM which is 60 folds more potent than acarbose. In addition, the MTT test using the three cell lines HCT-116, MDA-MB-231, and A549 showed that the target compounds have low cytotoxic effects with IC₅₀ values in the range of 60–280 μM, therefore they can be considered as safe compounds. Molecular docking studies predicted that the strong inhibitory activity of <strong>2A</strong> is related to the interactions generated by the three residues Asp282, Trp481, and Asp616 with the triazine core and hydrazide motif in the active site of the enzyme. The significant inhibitory effect of <strong>2A</strong> against α-glucosidase was also confirmed <em>in vivo</em>, where the compound showed equivalent activity to the standard drug acarbose on reducing blood glucose in the tested mice. In conclusion, this study introduces compound <strong>2A</strong> as a new lead compound with favorable cytotoxicity, strong α-glucosidase inhibitory activity and <em>in vivo</em> hypoglycemic effect, for future investigation in the treatment of diabetes mellitus.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100207"},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000797/pdfft?md5=9de0dfb2df03e62a5b57ea51f13b23da&pid=1-s2.0-S2772417424000797-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142039198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis and antitumor activity of 3,4,5-Trisubstituted Isoxazoles","authors":"Kanghui Duan ,&nbsp;Fuxing Tan ,&nbsp;Hongming Xie ,&nbsp;Haiwang Liu ,&nbsp;Yingjun Zhang ,&nbsp;Huanfeng Jiang ,&nbsp;Wanqing Wu","doi":"10.1016/j.ejmcr.2024.100203","DOIUrl":"10.1016/j.ejmcr.2024.100203","url":null,"abstract":"<div><p>In this study, 56 isoxazole derivatives were synthesized and their antitumor activity against 9 cancer cells, such as BXPC-3, MiaPaCa-2, PANC-1, MCF-7, HCT-116, HepG2, NCI-H460, A549 and B16 was detected. The results of pharmacological experiments indicated that most compounds exhibit good cytotoxicity against nine cancer cells. Among them, compound <strong>14</strong>–<strong>3</strong> has an IC₅₀ of 2.4 μM for colon cancer cells HCT-116, which shows the best effect and is better than the broad-spectrum drug 5-Fluorouracil (5-Fu) for the treatment of colon cancer. In addition, <strong>14</strong>–<strong>3</strong> induces apoptosis and leads to cell cycle arrest in the G2/M phase. Cytotoxicity tests on human normal hepatocytes LO2 also demonstrates that <strong>14</strong>–<strong>3</strong> is less toxic than 5-Fu with no obvious toxicity. These results suggest that <strong>14</strong>–<strong>3</strong> is a potential candidate for the development of anti-tumor drugs.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100203"},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277241742400075X/pdfft?md5=d9d5bb3d63fdd470bae8fe1359c4c765&pid=1-s2.0-S277241742400075X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microneedles in cosmetology: A SWOT analysis","authors":"Shweta Singh ,&nbsp;Rimpa Karmakar ,&nbsp;Devkant Pundir,&nbsp;Akash Singh,&nbsp;Sakshi Soni,&nbsp;Monika Vishwakarma,&nbsp;Arpana Purohit,&nbsp;Sushil K. Kashaw,&nbsp;Vandana Soni","doi":"10.1016/j.ejmcr.2024.100197","DOIUrl":"10.1016/j.ejmcr.2024.100197","url":null,"abstract":"<div><h3>Background</h3><p>Cosmetic microneedling has emerged as a popular minimally invasive technique. This systematic review employs the SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis framework to comprehensively evaluate the current landscape of cosmetic microneedles.</p></div><div><h3>Method</h3><p>The review incorporates a rigorous examination of peer-reviewed articles, the number of publications from the year 2008–2023, clinical trials, market products and devices available, and patents related to cosmetic microneedles. The selection criteria include relevance to SWOT analysis, publication quality, and recency. A systematic and transparent methodology is employed to ensure the inclusion of the most pertinent and reliable evidence available.</p></div><div><h3>Conclusion</h3><p>Microneedle systems in cosmetic applications reveal a dynamic landscape marked by strengths such as precise drug delivery and self-administration potential. However, these cutting-edge mechanisms face challenges, including concerns about skin damage and regulatory complexities. Opportunities lie in the targeted delivery capabilities across diverse cosmetic treatments, from hair growth to scar reduction and anti-wrinkle therapy. Incorporating artificial intelligence (AI) and machine learning into microneedling procedures has the potential to transform numerous aspects of cosmetic treatment. The insights gained from this analysis are relevant for practitioners, researchers, and industry professionals, guiding future research directions, technological advancements, and strategic decision-making in the cosmetic microneedling domain.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100197"},"PeriodicalIF":0.0,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000694/pdfft?md5=65c2e7c36a528447fd5fa7e2e1945413&pid=1-s2.0-S2772417424000694-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142099080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting capsaicin and nonivamide: Their analogs exert strong inhibitory activity against cholinesterases","authors":"Niels V. Heise,&nbsp;Jeremy Quast,&nbsp;René Csuk","doi":"10.1016/j.ejmcr.2024.100200","DOIUrl":"10.1016/j.ejmcr.2024.100200","url":null,"abstract":"<div><p>The scientific community has long been interested in capsaicin, and the extensive hunt for AChE and BChE enzyme inhibitors is still ongoing. In this investigation analogs of capsaicin, such as the pharmaceutical nonivamide, which is preferred in clinical settings for the topical treatment of pain, were explored in the search for appropriate inhibitors. Thus, to test their inhibitory effect on AChE and BChE, we synthesized a short series of derivatives derived from vanillylamide. Consequently, it was discovered that compounds <strong>12</strong>, <strong>34</strong>, and <strong>35</strong>, which have K_i values in the sub-micromolar concentration range, are especially effective inhibitors. Compound <strong>12</strong> demonstrated dual mixed-type (competitive/uncompetitive) inhibitory activity for both enzymes; compound <strong>34</strong> showed selective mixed-type inhibitory activity for AChE, and compound <strong>35</strong> was found to have selective uncompetitive activity for AChE.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100200"},"PeriodicalIF":0.0,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000724/pdfft?md5=c7581ccd38237ac9d42b9d9e9c8b2eb3&pid=1-s2.0-S2772417424000724-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142039581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}