European Journal of Medicinal Chemistry Reports最新文献_第3页

Synthesis, In vitro antimicrobial activity, and In silico bioinformatical approach of xanthone-fatty acid esters against Staphylococcus aureus, Escherichia coli, and Candida albicans

European Journal of Medicinal Chemistry Reports Pub Date : 2025-01-07 DOI: 10.1016/j.ejmcr.2025.100245

Yehezkiel Steven Kurniawan , Ervan Yudha , Jumina , Harno Dwi Pranowo , Eti Nurwening Sholikhah

{"title":"Synthesis, In vitro antimicrobial activity, and In silico bioinformatical approach of xanthone-fatty acid esters against Staphylococcus aureus, Escherichia coli, and Candida albicans","authors":"Yehezkiel Steven Kurniawan , Ervan Yudha , Jumina , Harno Dwi Pranowo , Eti Nurwening Sholikhah","doi":"10.1016/j.ejmcr.2025.100245","DOIUrl":"10.1016/j.ejmcr.2025.100245","url":null,"abstract":"<div><div>Microbial infection is gaining attention nowadays due to a high number of active cases and mortality rate. Because of that, research in finding new antimicrobial agents is urgently needed. In this work, we combined the chemical structure of 3-hydroxyxanthone and some fatty acids through ester linkage to form xanthyl laurate, xanthyl myristate, xanthyl palmitate, xanthyl stearate, and xanthyl oleate in 78.68–89.77 % yield. The <em>in vitro</em> antimicrobial assay revealed that xanthyl laurate exhibited the strongest antimicrobial activity with zone of inhibition of 11.0 ± 1.65, 9.43 ± 1.74, and 9.30 ± 1.37 mm against <em>Staphylococcus aureus</em>, <em>Escherichia coli</em>, and <em>Candida albicans</em>, respectively, which also higher than 3-hydoxyxanthone and lauric acid. Xanthyl laurate also yielded minimum inhibition concentration values of 31.25–62.50 μg/mL, which was 2 times lower than of 3-hydroxyxanthone. The structure-based bioinformatical approach indicated that ftsZ <em>S. aureus</em>, MAPK <em>E. coli</em>, and PDE <em>C. albicans</em> are the potential target for xanthyl laurate. Furthermore, both molecular docking and molecular dynamic simulations indicated good stability of xanthyl laurate in the active site of each protein receptor through hydrogen bond and other non-covalent interactions. The <em>in vitro</em> cytotoxicity assay against the NIH3T3 cell line showed that xanthyl laurate was non-toxic at 500 μg/mL with a cell viability percentage of 86.14 ± 1.38 %. This study reports that xanthyl laurate is the most potential antimicrobial agent based on the xanthone-fatty acid ester's structure against <em>S. aureus</em>, <em>E. coli</em>, and <em>C. albicans</em> in both <em>in vitro</em> and <em>in silico</em> assays.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"13 ","pages":"Article 100245"},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160277","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}

引用次数: 0

Epigallocatechin-gallate ameliorates polystyrene microplastics-induced oxido-inflammation and mitochondria-mediated apoptosis in testicular cells via modulation of Nrf2/HO-1, /mTOR/Atg-7, and Cx-43/NOX-1 levels

European Journal of Medicinal Chemistry Reports Pub Date : 2024-12-20 DOI: 10.1016/j.ejmcr.2024.100243

Mega Obukohwo Oyovwi , Emeka Williams Ugwuishi , Onoriode Andrew Udi , Adedeji David Atere , Arientare Rume Rotu , Emmanuel Igho Odokuma , Victor Oghenekparobo Emojevwe , Gideon Temitope Olowe , Eze Kingsley Nwangwa , Benneth Ben-Azu

{"title":"Epigallocatechin-gallate ameliorates polystyrene microplastics-induced oxido-inflammation and mitochondria-mediated apoptosis in testicular cells via modulation of Nrf2/HO-1, /mTOR/Atg-7, and Cx-43/NOX-1 levels","authors":"Mega Obukohwo Oyovwi , Emeka Williams Ugwuishi , Onoriode Andrew Udi , Adedeji David Atere , Arientare Rume Rotu , Emmanuel Igho Odokuma , Victor Oghenekparobo Emojevwe , Gideon Temitope Olowe , Eze Kingsley Nwangwa , Benneth Ben-Azu","doi":"10.1016/j.ejmcr.2024.100243","DOIUrl":"10.1016/j.ejmcr.2024.100243","url":null,"abstract":"<div><div>The study aimed to investigate the impact of Epigallocatechin-gallate (EGCG) on polystyrene microplastics (PS-MPs) induced reproductive anomalies in rats. To induce reproductive toxicity, PS-MPs were administered at a dose of 0.01 mg/kg/bw for several weeks. Following this, rats were treated with oral doses of 80 mg/kg/bw EGCG for 8 weeks. PS-MPs increase MDA levels while decreasing SOD, CAT, and GSH activity. EGCG administration reduces these effects. Inflammatory markers like NF-κB, IL-1β, TNF-α, NOX-1, and NLRP3 inflammasome are upregulated with PS-MPs but downregulated with EGCG treatment. Cx-43, Nrf2, HO-1, mTOR, and Atg-7 decrease with PS-MPs but increase with EGCG co-treatment. PS-MPs also increase NLRP3 levels, but EGCG treatment inhibits this effect. EGCG enhances sperm quality by raising motility, count, viability, and decreasing the ratio of aberrant and dead spermatozoa. Additional evidence for the reduced spermatogenesis was provided by histopathological scoring. Testicular tissue was subjected to PS-MP-induced oxidative stress, apoptosis, and inflammation; however, EGCG therapy reversed these effects and enhanced sperm quality. Overall, the PS-MPs-induced reproductive toxicity in rats appears to have potential for therapy with EGCG supplementation due to the modulation of Nrf2/HO-1, mTOR/Atg-7, and Cx-43/NOX-1 levels, as well as the prevention of mitochondria-mediated apoptosis and oxido-inflammation.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"13 ","pages":"Article 100243"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160323","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}

引用次数: 0

Preparation and pharmacological characterization of the enantiomers of the anticancer agent R/S-N-3-cyanophenyl-N'-(6-tert-butoxycarbonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)urea: Identification of the R-enantiomer as the active eutomer

European Journal of Medicinal Chemistry Reports Pub Date : 2024-12-19 DOI: 10.1016/j.ejmcr.2024.100244

Michael Schnekenburger , Eric Goffin , Matthieu Schoumacher , Nikolay Tumanov , Ange Mouithys-Mickalad , Pascal de Tullio , Johan Wouters , Philippe Lebrun , Marc Diederich , Bernard Pirotte

{"title":"Preparation and pharmacological characterization of the enantiomers of the anticancer agent R/S-N-3-cyanophenyl-N'-(6-tert-butoxycarbonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)urea: Identification of the R-enantiomer as the active eutomer","authors":"Michael Schnekenburger , Eric Goffin , Matthieu Schoumacher , Nikolay Tumanov , Ange Mouithys-Mickalad , Pascal de Tullio , Johan Wouters , Philippe Lebrun , Marc Diederich , Bernard Pirotte","doi":"10.1016/j.ejmcr.2024.100244","DOIUrl":"10.1016/j.ejmcr.2024.100244","url":null,"abstract":"<div><div>R/S-N-3-cyanophenyl-N'-(6-tert-butoxycarbonylamino-3,4-dihydro-2,2-dimethyl-2<em>H</em>-1-benzopyran-4-yl)urea (BPDZ 711, <strong>4</strong>) initially designed as a K<sub>ATP</sub> channel opener, was found to exhibit diverse biological activities. The compound inhibited insulin release from rat pancreatic islets, indicating a potential effect on glucose metabolism. Oxygraphy measurements on chronic myeloid leukemia (CML) K-562 cells revealed an impact on cellular respiration. Additionally, the compound demonstrated inhibitory activity on histone deacetylase class III enzymes (sirtuins), linking metabolic and epigenetic regulation. This was corroborated by its effect on protein acetylation and modulation of the extracellular pH of treated CML cells. Alterations in CML cells' nuclear morphology and the release of high-mobility group box 1 (HMGB1) protein confirmed mechanisms related to cellular stress and immunogenic cell death. BPDZ 711 preserved the viability of peripheral blood mononuclear cells, thus demonstrating excellent differential toxicity.</div><div>Since BPDZ 711 is a racemate, the present study focused on the preparation of the two enantiomers and examined the possibility that each isomer could display a distinct pharmacological profile. Our data revealed that the R-enantiomer (<strong>5</strong>) of BPDZ 711 was consistently the most biologically active compound (eutomer), making it the reference compound for future drug discovery and development.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"13 ","pages":"Article 100244"},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160324","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}

引用次数: 0

Photochemical internalization of mRNA using a photosensitizer and nucleic acid carriers

European Journal of Medicinal Chemistry Reports Pub Date : 2024-12-09 DOI: 10.1016/j.ejmcr.2024.100242

Hayaki Maemoto , Ryohei Suzaki , Kazunori Watanabe , Keiji Itaka , Takashi Ohtsuki

{"title":"Photochemical internalization of mRNA using a photosensitizer and nucleic acid carriers","authors":"Hayaki Maemoto , Ryohei Suzaki , Kazunori Watanabe , Keiji Itaka , Takashi Ohtsuki","doi":"10.1016/j.ejmcr.2024.100242","DOIUrl":"10.1016/j.ejmcr.2024.100242","url":null,"abstract":"<div><div>mRNA has great potential for therapeutic applications because it can encode a variety of proteins and antigens, in addition to advantages over DNA in terms of gene expression without genomic integration, nuclear localization, or transcription. However, therapeutic applications of mRNA require safe and effective delivery into target cells. Therefore, we aimed to investigate photochemical internalization (PCI) as a promising strategy for delivering mRNA to target cells. In this strategy, mRNA is taken up into cells by endocytosis, accumulates in endosomes, and is released in a light-dependent manner from the endosomes using an endosome-accumulating photosensitizer, aluminum phthalocyanine disulfonate (AlPcS<sub>2a</sub>), in combination with nucleic acid carrier molecules. We compared the efficacy of various nucleic acid carriers, including branched polyethyleneimine (bPEI) and poly{N'-[N-(2-aminoethyl)-2-aminoethyl] aspartamide} (PAsp(DET)) under the same conditions for PCI-based mRNA delivery. Our results indicated that bPEI and PAsp(DET) at low N/P ratios exhibited efficient light-enhancement of mRNA expression by PCI with AlPcS<sub>2a</sub>. Notably, bPEI exhibited the highest light-dependent mRNA delivery among the carriers evaluated (including cationic polymers, cationic peptides, and lipids), whereas PAsp(DET) showed promise for clinical use because of its lower toxicity compared with bPEI. This PCI strategy allows effective cytosolic mRNA delivery at low N/P ratios, thereby reducing cationic carrier molecule-induced cytotoxicity. This method allows spatiotemporal control of protein expression and holds potential for novel light-dependent mRNA therapies. Overall, this study provided valuable insights into optimizing mRNA delivery systems for therapeutic applications.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"13 ","pages":"Article 100242"},"PeriodicalIF":0.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160280","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}

引用次数: 0

Synthesis and in vitro/in silico evaluation of the antimalarial activity of potential amino-quinoline derivatives

European Journal of Medicinal Chemistry Reports Pub Date : 2024-12-02 DOI: 10.1016/j.ejmcr.2024.100241

Moussa Touré , Abdoulaye Gassama , Oumar Sambou , Christian Cavé , Sandrine Cojean

{"title":"Synthesis and in vitro/in silico evaluation of the antimalarial activity of potential amino-quinoline derivatives","authors":"Moussa Touré , Abdoulaye Gassama , Oumar Sambou , Christian Cavé , Sandrine Cojean","doi":"10.1016/j.ejmcr.2024.100241","DOIUrl":"10.1016/j.ejmcr.2024.100241","url":null,"abstract":"<div><div>In this study, a series of <em>N</em>-arylamino-7-chloroquinolines were synthesized via an alkylation reaction involving aniline derivatives <strong>(2)</strong> and 4,7-dichloroquinoline <strong>(1)</strong>. Additionally, the synthesis of a library of <em>N</em>-aryl-<em>N</em>-benzylamino-7-chloroquinoline analogues, modified on the aniline nitrogen, has also reported. A structure-activity relationship (SAR) study was conducted to evaluate the biological efficacy and safety of these derivatives against chloroquine-sensitive (<em>Pf</em>3D7) and chloroquine-resistant (<em>Pf</em>W2) <em>Plasmodium falciparum</em> strains. Compounds <strong>5i</strong> and <strong>5c</strong> showed promising efficacy against the <em>Pf</em>3D7 strain with IC<sub>50</sub> values of 0.25 μM and 0.54 μM, respectively, while compound <strong>5l</strong> demonstrated significant activity against the <em>Pf</em>W2 strain with an IC<sub>50</sub> of 5.82 μM. The cytotoxicity of these compounds was also evaluated on HUVEC cell lines. Additionally, their pharmacological and pharmacokinetic (ADME) properties were studied to predict their fate and identify promising candidates for further clinical studies.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"13 ","pages":"Article 100241"},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160325","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}

引用次数: 0

Corrigendum to “The pyrazolo[4,3-c]pyrazole core as a novel and versatile scaffold for developing dual DYRK1A-CLK1 inhibitors targeting key processes of Alzheimer's disease pathology” [Europ. J. Med. Chem. Rep. 12 (2024) 100193]

European Journal of Medicinal Chemistry Reports Pub Date : 2024-12-01 DOI: 10.1016/j.ejmcr.2024.100222

Vaia-Argyro Bakalakou , Barbara Mavroidi , Amalia D. Kalampaliki , Béatrice Josselin , Stéphane Bach , Alexios-Leandros Skaltsounis , Panagiotis Marakos , Nicole Pouli , Maria Pelecanou , Vassilios Myrianthopoulos , Sandrine Ruchaud , Ioannis K. Kostakis

引用次数: 0

Novel synthesized seleno-glycoconjugates as cosmeceutical ingredients: Antioxidant activity and in vitro skin permeation 作为药妆成分的新型合成硒糖共轭物：抗氧化活性和体外皮肤渗透性

European Journal of Medicinal Chemistry Reports Pub Date : 2024-11-12 DOI: 10.1016/j.ejmcr.2024.100240

Giovanna Cimmino , Mauro De Nisco , Cristina Alonso , Claudia Gravina , Vincenzo Piscopo , Reinier Lemos , Luisa Coderch , Simona Piccolella , Severina Pacifico , Silvana Pedatella

{"title":"Novel synthesized seleno-glycoconjugates as cosmeceutical ingredients: Antioxidant activity and in vitro skin permeation","authors":"Giovanna Cimmino , Mauro De Nisco , Cristina Alonso , Claudia Gravina , Vincenzo Piscopo , Reinier Lemos , Luisa Coderch , Simona Piccolella , Severina Pacifico , Silvana Pedatella","doi":"10.1016/j.ejmcr.2024.100240","DOIUrl":"10.1016/j.ejmcr.2024.100240","url":null,"abstract":"<div><div>Following recent successful results in the search for innovative semi-synthetic cosmeceutical Se-glycoconjugates, the work reported herein explores the development and evaluation of second-generation selenosugar-linked hydroxycinnamic acids as new potential cosmeceutical ingredients. Utilizing a Pummerer-like rearrangement for C1-acetylation, these novel compounds were synthesized and characterized using NMR spectroscopy and HRMS, confirming their structures and purity. The biological evaluation focused on their radical scavenging preliminary screening, and cytotoxic and antioxidant activities in human immortalized keratinocytes, revealing significant potential for use in skin care formulations aimed at counteracting oxidative stress and promoting skin health. Cellular uptake studies conducted on HaCaT keratinocytes using UHPLC-QqTOF-MS metabolomics demonstrated effective internalization of these compounds, which is crucial for their efficacy as topical agents. Furthermore, percutaneous absorption tests using the Franz diffusion cell method and subsequent HPLC-DAD analysis provided insights into the compound skin permeation capabilities, a critical factor for their practical application in cosmeceuticals.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100240"},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142651714","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}

引用次数: 0

Use of radiopharmaceuticals in the diagnosis of neurodegenerative diseases 使用放射性药物诊断神经退行性疾病

European Journal of Medicinal Chemistry Reports Pub Date : 2024-11-04 DOI: 10.1016/j.ejmcr.2024.100239

Anna Tempesta , Anna Tolomeo , Azzurra Stefanucci , Lorenza Marinaccio , Adriano Mollica

引用次数: 0

Gold nanobiosensors and Machine Learning: Pioneering breakthroughs in precision breast cancer detection 金纳米生物传感器和机器学习：乳腺癌精准检测的开创性突破

European Journal of Medicinal Chemistry Reports Pub Date : 2024-10-30 DOI: 10.1016/j.ejmcr.2024.100238

Soheil Sadr , Ashkan Hajjafari , Abbas Rahdar , Sadanand Pandey , Parian Poorjafari Jafroodi , Narges Lotfalizadeh , Mahdi Soroushianfar , Shahla Salimpour Kavasebi , Zelal Kharaba , Sonia Fathi-karkan , Hassan Borji

{"title":"Gold nanobiosensors and Machine Learning: Pioneering breakthroughs in precision breast cancer detection","authors":"Soheil Sadr , Ashkan Hajjafari , Abbas Rahdar , Sadanand Pandey , Parian Poorjafari Jafroodi , Narges Lotfalizadeh , Mahdi Soroushianfar , Shahla Salimpour Kavasebi , Zelal Kharaba , Sonia Fathi-karkan , Hassan Borji","doi":"10.1016/j.ejmcr.2024.100238","DOIUrl":"10.1016/j.ejmcr.2024.100238","url":null,"abstract":"<div><div>Breast cancer is still one of the major health concerns of today's world. In light of such a scenario, regular improvement in the detection technique is crucial to meet better early diagnosis and treatment outcomes. This present work places much emphasis on gold nanobiosensors, which might be of utmost use in improving breast cancer diagnosis by the excellent sensitivity and specificity they offer for the identification of cancer-related biomarkers. These sensors take advantage of the unique optical and electric properties that gold nanoparticles have, enabling them to achieve an accurate molecular level of detection. Gold nanobiosensors have been significantly developed through innovations like signal amplification and surface functionalization, integrated with the use of advanced imaging techniques. Efforts have been done to enhance their biocompatibility, stability, and scalability for clinical applications. The integration of gold nanobiosensors with emerging technologies, including microfluidics and machine learning, opens new perspectives for personalized diagnostics and point-of-care testing in resource-constrained settings. However, further challenges lie ahead: to enhance manufacturing techniques, to conduct large-scale clinical trials, and to overcome limitations in regulations before widespread clinical applications. Continuous studies and technological advances indicate that gold nanobiosensors have the potential to significantly improve early diagnosis of breast cancer, reducing mortality rates and enhancing the care of patients.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100238"},"PeriodicalIF":0.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142651712","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}

引用次数: 0

A reagent-free, sequence-dependent in situ peptide self-cyclization strategy under physiological condition 生理条件下的无试剂、序列依赖性原位多肽自环化策略

European Journal of Medicinal Chemistry Reports Pub Date : 2024-10-24 DOI: 10.1016/j.ejmcr.2024.100236

Nibedita Ghosh , Lal Mohan Kundu

{"title":"A reagent-free, sequence-dependent in situ peptide self-cyclization strategy under physiological condition","authors":"Nibedita Ghosh , Lal Mohan Kundu","doi":"10.1016/j.ejmcr.2024.100236","DOIUrl":"10.1016/j.ejmcr.2024.100236","url":null,"abstract":"<div><div>Cyclic peptides are an important class of bioactive molecules used as drugs as well as biomolecular probes. Peptide cyclization under the physiological environment, without added chemicals or reagents, would be a highly useful technique for in situ applications. A simple, highly efficient, and green procedure for side-chain to side-chain in situ peptide cyclization is established here at the physiological condition. The methodology further allows the release of small biologically active molecules through peptide self-cyclization. Bioactive molecules, as well as other organic leaving groups (having primary or secondary alcohol as a functional group), were conjugated to a short peptide RXE sequence (X = Pro/Ala/Gly). The peptides were designed to undergo cyclization under physiological conditions and release the covalently attached chemotherapeutic drug and nucleobases, in a controlled manner. In vitro studies were performed in detail, with optimized physiological parameters, to understand the kinetics as well as the mechanism of self-cyclization. The mechanism of action was investigated by HPLC and ESI-Mass spectrometry. The conformational change, due to cyclization of the peptides, was monitored by CD spectroscopy. The present concept of peptide self-cyclization leading to a bond cleavage could be a potential method of delivery of small, bioactive molecules such as chemotherapeutic drugs.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100236"},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532748","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}

引用次数: 0