European Journal of Medicinal Chemistry Reports最新文献

{"title":"The isoquinoline derivative \"CYNOVID\" as a prospective anti-SARS-CoV-2 agent: An expanded investigative computational study","authors":"Amgad M. Rabie ,&nbsp;Imane Yamari ,&nbsp;Samir Chtita","doi":"10.1016/j.ejmcr.2024.100214","DOIUrl":"10.1016/j.ejmcr.2024.100214","url":null,"abstract":"<div><div>Isoquinoline compounds holding some nucleosidic structural hallmarks are considered possible attractive options for effectively combating the different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and their associated disease, the coronavirus disease 2019 (COVID-19). The CYNOVID molecule ((<em>S</em>)-6-chloro-2-{[(1-cyanocyclopropyl)methyl]sulfonyl}-<em>N</em>-(isoquinolin-4-yl)-1,2,3,4-tetrahydroisoquinoline-4-carboxamide) is a recently-discovered isoquinoline compound with potent anticoronaviral activities against several SARS-CoV-2 variants according to different antiviral cellular assays. CYNOVID nonspecifically binds to the main protease (M^pro) enzyme of several coronaviruses. As an extensive continued effort to develop this potential anti-SARS-CoV-2 agent and examine its nonspecific broad potential to be an effective broad-spectrum anti-COVID-19 therapy, a new comprehensive <em>in-silico</em> research study was proposed and designed to explore the inhibitory abilities of this isoquinoline derivative against the two major highly-conserved SARS-CoV-2 replication enzymes (i.e., the SARS-CoV-2 replication proteins other than M^pro), which are the RNA-dependent RNA polymerase (RdRp) and 3′-to-5′ exoribonuclease (ExoN) enzymes. The various computational results of the present study significantly supported the previous biochemical/biological findings as well as the newly-suggested multiple-targeting hypothesis, disclosing the possible nonspecific anticoronaviral activities of this promising experimental agent, CYNOVID, against nearly any coronaviral-2 variants and, probably, any future coronaviral species, e.g., SARS-CoV-3.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100214"},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699513","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":"“Quinoline analogues and nanocarrier systems: A dual approach to anti-tubercular therapy\"","authors":"Satendra Kumar ,&nbsp;Niranjan Kaushik ,&nbsp;Jagdish Kumar Sahu ,&nbsp;Surendra Jatav","doi":"10.1016/j.ejmcr.2024.100212","DOIUrl":"10.1016/j.ejmcr.2024.100212","url":null,"abstract":"<div><p>Mycobacterium tuberculosis (MTB) is the agent that causes tuberculosis (TB), the most lethal infectious illness that affects around one-third of the global population and has resulted in 1.5 million fatalities in recent years. As of right now, sensitive MTB strain-caused tuberculosis can be successfully treated with short-term tuberculosis therapy regimens. However, an increasing issue in many nations is tuberculosis brought on by multidrug-resistant (MDR) and extensively drug-resistant (XDR) MTB strains.</p><p>In recent years, TB has remained major global public health issue. The screening of novel bioactive compounds with new targets and alternative mechanisms of action is urgently needed. The WHO is working to eliminate tuberculosis globally and has set the goal of reducing TB case by 90 % and incidence 80 % by 2035 as part of the sustainable development Goals. Quinoline-based heterocyclic compounds have become quite important in medical chemistry. Due to the exceptional outcomes of their derivatives, quinoline hydrazone scaffold is crucial in the creation of anti-tubercular drugs. The synthetic flexibility of quinoline, which enables the creation of a vast variety of structurally diverse hydrazone derivatives and their metal complexes, has further aided this wide range of biological and biochemical activities.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100212"},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000840/pdfft?md5=44c66b3cb7d41866b98dd1dd90f691fb&pid=1-s2.0-S2772417424000840-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241348","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, characterization, and biological evaluation of coumarin-nitric oxide donor hybrids as anti-tubercular agents","authors":"Afeez I. Kareem,&nbsp;Sarel F. Malan,&nbsp;Erika Kapp,&nbsp;Sean Shamido,&nbsp;Jacques Joubert","doi":"10.1016/j.ejmcr.2024.100211","DOIUrl":"10.1016/j.ejmcr.2024.100211","url":null,"abstract":"<div><p>This study presents a series of coumarin nitric oxide donor hybrids that were synthesized, and characterized using FT-IR, H NMR, C NMR, and HR-MS techniques. Initial screening for anti-tubercular activity was conducted against <em>Mycolicibacterium smegmatis MC</em>^<em>2</em><em>155</em> (<em>M.smeg</em>) under both nutrient-rich and nutrient-poor conditions. Under nutrient-rich conditions, little inhibition was observed. However, four compounds (<strong>1e</strong>, <strong>2o</strong>, <strong>3f</strong>, and <strong>5e</strong>) demonstrated notable antiproliferative activity under nutrient-poor conditions, with inhibition rates exceeding 95 % at a 50 μM concentration. Subsequent testing of these compounds on <em>Mycobacterium tuberculosis</em> (<em>M.tb)</em> under nutrient-rich conditions showed inhibition rates ranging from 11 % to 37 % at 50 μM. These results indicate that the coumarin nitric oxide donor hybrids are potentially effective in nutrient-limited environments, similar to the intracellular conditions faced by <em>M.tb</em>. <em>In silico</em> cytotoxicity predictions, compared with rifampicin, indicated potentially low toxicity for these compounds. Further optimization and studies are needed to enhance their efficacy under normal conditions, which could lead to the development of new therapeutic strategies against tuberculosis.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100211"},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000839/pdfft?md5=787f13a81d1a5e770c8ee2ce13838dee&pid=1-s2.0-S2772417424000839-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142151804","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":"Advances in synthesis, medicinal properties and biomedical applications of pyridine derivatives: A comprehensive review","authors":"Duryodhan Sahu ,&nbsp;P.S. Rama Sreekanth ,&nbsp;Prasanta Kumar Behera ,&nbsp;Manoj Kumar Pradhan ,&nbsp;Amit Patnaik ,&nbsp;Sachin Salunkhe ,&nbsp;Robert Cep","doi":"10.1016/j.ejmcr.2024.100210","DOIUrl":"10.1016/j.ejmcr.2024.100210","url":null,"abstract":"<div><p>Pyridine derivatives have emerged as promising candidates in the field of biomedical research, showcasing a wide array of applications in drug development and therapeutic interventions. The recent advances in the design and utilization of pyridine derivatives, focusing on their diverse roles in biomedical applications is the key understanding in this study. The versatility of pyridine-based compounds has been leveraged to address various challenges in the realms of pharmaceuticals and medicinal chemistry, offering innovative solutions for improved healthcare outcomes. This review encompasses the synthesis methodologies of pyridine derivatives, elucidating key synthetic strategies that enable the tailoring of these compounds for specific biomedical purposes and medicinal properties. This underscores the recent advancements in understanding the pharmacokinetics and pharmacodynamics of pyridine derivatives, emphasizing their potential impact on the future landscape of biomedical research. The synthesis and application of these compounds represent a dynamic frontier in drug development, offering innovative solutions to address unmet medical needs and propel the field toward more effective and personalized therapies. Pyridine derivatives play an important role in bio-imaging applications for the diagnosis of various diseases. Pyridine-based macromolecules have great potential for the efficient and specific delivery of drugs.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100210"},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000827/pdfft?md5=810fec813bfb8c4e372565f0d1c88f7e&pid=1-s2.0-S2772417424000827-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158134","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, 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}