MedChemComm最新文献

{"title":"On-resin synthesis of Lanreotide epimers and studies of their structure–activity relationships†","authors":"Arnab Chowdhury, Nitesh Mani Tripathi, Rohit Jadav, Vinod Gour, Parva Purohit and Anupam Bandyopadhyay","doi":"10.1039/D4MD00338A","DOIUrl":"10.1039/D4MD00338A","url":null,"abstract":"<p >Peptide drugs often accompany epimeric impurities (isomers). Therefore, efficient chemical synthesis of epimers is critical to identify them correctly and investigate their biological activities. Here, we report the rapid synthesis and structure–activity relationship (SAR) studies of eight possible epimers of a somatostatin synthetic analog (SSA), lanreotide (LAN). SPPS and the subsequent on-resin rapid disulfide closure method offered &gt;90% conversion yield for all epimers (<strong>P1–P8</strong>). Further, we developed an analytical method to separate these epimers, which enabled the profiling of five epimeric impurities in the API, purchased for Somatuline generic formulations. In SAR studies, most LAN epimers revealed compromised antiproliferative activity, while the <strong>P7</strong> epimer retained antiproliferative activity similar to LAN API, as supported by <em>in silico</em> SAR studies in detail. Additionally, <strong>P7</strong> showed serum stability nearly identical to LAN, suggesting that drug epimers could be a potential API. Current studies will further encourage the development of novel SSA scaffolds.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 8","pages":" 2766-2772"},"PeriodicalIF":3.597,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141612357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, inhibitory activity, and molecular simulations study for d-glucose-conjugated thioureas containing pyrimidine ring as multitarget inhibitors against α-amylase, α-glucosidase, DDP-4, and PTP1B in Type 2 diabetes mellitus†","authors":"Vu Ngoc Toan, Do Son Hai, Hoang Thi Kim Van, Nguyen Minh Tri, Duong Ngoc Toan, Nguyen Thi Thanh Mai and Nguyen Dinh Thanh","doi":"10.1039/D4MD00334A","DOIUrl":"10.1039/D4MD00334A","url":null,"abstract":"<p >A series of tetra-<em>O</em>-acetyl-α-<small>D</small>-glucopyranosyl thioureas <strong>8a–l</strong> of substituted 2-aminopyrimidines <strong>4a–l</strong> have been designed and synthesized. The latter were prepared from corresponding chalcones <strong>3a–l</strong> of <em>p</em>-bromoacetophenone and appropriate substituted benzaldehydes by their reaction with guanidine. The target thiourea compounds <strong>8a–l</strong> exhibited significant inhibitory activity <em>in vitro</em> against enzymes that were related to type 2 diabetes mellitus, including α-amylase, α-glucosidase, DPP-4, and PTP1B. Amongst these thioureas, compound <strong>8k</strong> with an <em>ortho</em>-methoxy group was the most potential enzyme inhibitor against α-amylase with an IC<small>₅₀</small> value of 9.72 ± 0.34 μM. Its <em>meta</em>-isomer <strong>8j</strong> was the strongest inhibitor against α-glucosidase with IC<small>₅₀</small> = 9.73 ± 0.72 μM. In the inhibition against DPP-4, compound <strong>8f</strong> with a <em>para</em>-bromo substituent exhibited the strongest activity with an IC<small>₅₀</small> value of 2.53 ± 0.03 nM. In the inhibition against PTP1B, compound <strong>8h</strong> with a <em>para</em>-isopropyl substituent had the strongest inhibitory activity with an IC<small>₅₀</small> value of 2.74 ± 0.03 μM. The enzyme kinetics of the most active compounds, including <strong>8j</strong>, <strong>8f</strong> and <strong>8h</strong> against α-glucosidase, DPP-4, and PTP1B, respectively, were studied. The obtained results showed that <strong>8j</strong> was a competitive α-glucosidase inhibitor with an inhibitory constant <em>K</em><small>_I</small> value of 9.31 μM. Compound <strong>8f</strong> was a non-competitive inhibitor for DDP-4 with an inhibitory constant <em>K</em><small>_I</small> value of 12.57 μM. Compound <strong>8h</strong> was also a non-competitive inhibitor for DDP-4 with an inhibitory constant <em>K</em><small>_I</small> value of 12.41 μM. The cytotoxicity of the most active compounds, including <strong>8f</strong> and <strong>8k</strong> (against α-amylase), <strong>8i</strong> and <strong>8j</strong> (against α-glucosidase), <strong>8a</strong>, <strong>8f</strong>, and <strong>8g</strong> (against DPP-4), and <strong>8d</strong>, <strong>8f</strong>, and <strong>8h</strong> (against PTP1B) was screened. The obtained cytotoxicity showed that all tested inhibitors were noncytotoxic to human normal cell line 3T3. Induced fit docking simulations of all synthesized compounds <strong>8a–l</strong> were performed on four enzymes 4W93 (for α-amylase), 3TOP (for α-glucosidase), 3W2T (for DPP-4), and 1NNY (for PTP1B). Key interactions of each of these ligands with residues in the active pocket of each studied enzyme have been shown.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 10","pages":" 3395-3417"},"PeriodicalIF":3.597,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current status and prospects of MOFs loaded with H2O2-related substances for ferroptosis therapy","authors":"Yu Deng, Sida Huang, Guanming Jiang, Luyi Zhou, Alireza Nezamzadeh-Ejhieh, Jianqiang Liu and Zhikun Zhou","doi":"10.1039/D4MD00261J","DOIUrl":"10.1039/D4MD00261J","url":null,"abstract":"<p >Ferroptosis is a programmed cell death mechanism characterized by the accumulation of iron (Fe)-dependent lipid peroxides within cells. Ferroptosis holds excellent promise in tumor therapy. Metal–organic frameworks (MOFs) offer unique advantages in tumor ferroptosis treatment due to their high porosity, excellent stability, high biocompatibility, and targeting capabilities. Inducing ferroptosis in tumor cells primarily involves the production of reactive oxygen species (ROS), like hydroxyl radicals (˙OH), through iron-mediated Fenton reactions. However, the intrinsic H<small>₂</small>O<small>₂</small> levels in tumor cells are often insufficient to sustain prolonged consumption, limiting therapeutic efficacy if ˙OH production is inadequate. Therefore, catalyzing or supplementing the intracellular H<small>₂</small>O<small>₂</small> levels in tumor cells is essential for inducing ferroptosis by nanoscale metal–organic frameworks. This article reviews the biological characteristics and molecular mechanisms of ferroptosis, introduces H<small>₂</small>O<small>₂</small>-related substances, and reviews MOF-based nanoscale strategies for enhancing intracellular H<small>₂</small>O<small>₂</small> levels in tumor cells. Finally, the challenges and prospects of this approach are discussed, aiming to provide insights into improving the effectiveness of ferroptosis induced by MOFs.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 9","pages":" 2996-3016"},"PeriodicalIF":3.597,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141771808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of a new series of 4-pyrazolylquinolinones with apoptotic antiproliferative effects as dual EGFR/BRAFV600E inhibitors†","authors":"Lamya H. Al-Wahaibi, Bahaa G. M. Youssif, Hesham A. Abou-Zied, Stefan Bräse, Alan B. Brown, Hendawy N. Tawfeek and Essmat M. El-Sheref","doi":"10.1039/D4MD00230J","DOIUrl":"10.1039/D4MD00230J","url":null,"abstract":"<p >The current study focuses on developing a single molecule that acts as an antiproliferative agent with dual or multi-targeted action, reducing drug resistance and adverse effects. A new series of 4-pyrazolylquinolin-2-ones (<strong>5a–j</strong>) with apoptotic antiproliferative effects as dual EGFR/BRAF<small>^V600E</small> inhibitors were designed and synthesized. Compounds <strong>5a–j</strong> were investigated for their cell viability effect against a normal cell line (MCF-10A). Results showed that none of the compounds were cytotoxic, and all <strong>5a–j</strong> demonstrated more than 90% cell viability at 50 μM concentration. Using erlotinib as a reference, the MTT assay investigated the antiproliferative impact of targets <strong>5a–j</strong> against four human cancer cell lines. Compounds <strong>5e</strong>, <strong>5f</strong>, <strong>5h</strong>, <strong>5i</strong>, and <strong>5j</strong> were the most potent antiproliferative agents with GI<small>₅₀</small> values of 42, 26, 29, 34, and 37 nM, making compounds <strong>5f</strong> and <strong>5h</strong> more potent than erlotinib (GI<small>₅₀</small> = 33 nM). Moreover, compounds <strong>5e</strong>, <strong>5f</strong>, <strong>5h</strong>, <strong>5i</strong>, and <strong>5j</strong> were further investigated as dual EGFR/BRAF<small>^V600E</small> inhibitors, and results revealed that compounds <strong>5f</strong>, <strong>5h</strong>, and <strong>5i</strong> are potent antiproliferative agents that act as dual EGFR/BRAF<small>^V600E</small> inhibitors. Cell cycle analysis and apoptosis detection revealed that compound <strong>5h</strong> displaying cell cycle arrest at the G1 transition could induce apoptosis with a high necrosis percentage. Docking studies revealed that compound <strong>5f</strong> exhibited a strong affinity for EGFR and BRAF<small>^V600E</small>, with high docking scores of −8.55 kcal mol<small>⁻¹</small> and −8.22 kcal mol<small>⁻¹</small>, respectively. Furthermore, the ADME analysis of compounds <strong>5a–j</strong> highlighted the diversity in their pharmacokinetic properties, emphasizing the importance of experimental validation.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 7","pages":" 2538-2552"},"PeriodicalIF":3.597,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141506032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical synthesis and immunological evaluation of cancer vaccines based on ganglioside antigens and α-galactosylceramide†","authors":"Cecilia Romanò, Hao Jiang, Sahar Tahvili, Peng Wei, Ulrik B. Keiding, Gael Clergeaud, Sarah Line Skovbakke, Anne Louise Blomberg, Lise Hafkenscheid, Jonas R. Henriksen, Thomas L. Andresen, Steffen Goletz, Anders E. Hansen, Dennis Christensen and Mads H. Clausen","doi":"10.1039/D4MD00387J","DOIUrl":"10.1039/D4MD00387J","url":null,"abstract":"<p >iNKT cells – often referred as the “Swiss Army knife” of the immune system – have emerged as central players in cancer vaccine therapies. Glycolipids activating iNKT cells, such as α-galactosylceramide (αGalCer), can enhance the immune response against co-delivered cancer antigens and have been applied in the design of self-adjuvanting anti-tumor vaccines. In this context, this work focuses on the chemical synthesis of ganglioside tumor-associated carbohydrate antigens (TACAs), namely GM3 and (Neu5Gc)GM3 antigens, their conjugation to αGalCer, and their formulation into liposomes as an efficient platform for their <em>in vivo</em> delivery. Liposomes containing GM3–αGalCer, (Neu5Gc)GM3–αGalCer, and equimolar amounts of the two conjugates have been fully characterized and their ability to activate iNKT cell has been confirmed <em>ex vivo</em> in mouse and human cell assays. The candidates were tested in <em>in vivo</em> immunization studies, demonstrating an ability to induce both T<small>_H</small>1 and T<small>_H</small>2 cytokines leading to the production of all subclasses of IgG antibodies. Notably, the study also demonstrated that serum antibodies raised against the two TACAs, alone and in combination, were cross-reactive. This finding has consequences for future vaccine designs – even if a highly tumor-selective antigen is chosen, the resulting antibody response may be broader than anticipated.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 8","pages":" 2718-2728"},"PeriodicalIF":3.597,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/md/d4md00387j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141546771","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 of novel coumarin triazolyl and phenoxyphenyl triazolyl derivatives targeting amyloid beta aggregation-mediated oxidative stress and neuroinflammation for enhanced neuroprotection†","authors":"Satsawat Visansirikul, Suthira Yanaso, Yingrak Boondam, Kanjanawadee Prasittisa, Brompoj Prutthiwanasan, Sumet Chongruchiroj and Kittisak Sripha","doi":"10.1039/D4MD00270A","DOIUrl":"10.1039/D4MD00270A","url":null,"abstract":"<p >This study involved designing, synthesizing, and evaluating the protective potential of compounds on microglial cells (BV-2 cells) and neurons (SH-SY5Y cells) against cell death induced by Aβ<small>_1–42</small>. It aimed to identify biologically specific activities associated with anti-Aβ aggregation and understand their role in oxidative stress initiation and modulation of proinflammatory cytokine expression. Actively designed compounds <strong>CE5</strong>, <strong>CA5</strong>, <strong>PE5</strong>, and <strong>PA5</strong> showed protective effects on BV-2 and SH-SY5Y cells, with cell viability ranging from 60.78 ± 2.32% to 75.38 ± 2.75% for BV-2 cells and 87.21% ± 1.76% to 91.55% ± 1.78% for SH-SY5Y cells. The transformation from ester in <strong>CE5</strong> to amide in <strong>CA5</strong> resulted in significant antioxidant properties. Molecular docking studies revealed strong binding of <strong>CE5</strong> to critical Aβ aggregation regions, disrupting both intra- and intermolecular formations. TEM assessment supported <strong>CE5</strong>'s anti-Aβ aggregation efficacy. Structural variations in <strong>PE5</strong> and <strong>PA5</strong> had diverse effects on IL-1β and IL-6, suggesting further specificity studies for Alzheimer's disease. Log <em>P</em> values suggested potential blood–brain barrier permeation for <strong>CE5</strong> and <strong>CA5</strong>, indicating suitability for CNS drug development. <em>In silico</em> ADMET and toxicological screening revealed that <strong>CE5</strong>, <strong>PA5</strong>, and <strong>PE5</strong> have favorable safety profiles, while <strong>CA5</strong> shows a propensity for hepatotoxicity. According to this prediction, coumarin triazolyl derivatives are likely to exhibit mutagenicity. Nevertheless, <strong>CE5</strong> and <strong>CA5</strong> emerge as promising lead compounds for Alzheimer's therapeutic intervention, with further insights expected from subsequent <em>in vivo</em> studies.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 8","pages":" 2745-2765"},"PeriodicalIF":3.597,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141568320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, and structure–activity relationship studies of 6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole derivatives as necroptosis inhibitors†","authors":"Zechen Jin, Yang Dai, Yinchun Ji, Xia Peng, Wenhu Duan, Jing Ai and Hefeng Zhang","doi":"10.1039/D4MD00265B","DOIUrl":"10.1039/D4MD00265B","url":null,"abstract":"<p >The development of necroptosis inhibitors has emerged as a promising strategy to effectively mitigate necroptosis-related inflammatory diseases, neurodegenerative diseases, and cancers. In this paper, we reported a series of 6,7-dihydro-5<em>H</em>-pyrrolo[1,2-<em>b</em>][1,2,4]triazole derivatives as potent necroptosis inhibitors. The representative compound <strong>26</strong> displayed potent anti-necroptotic activity in both human and mouse cellular assays and exhibited potent inhibitory activity against receptor-interacting protein kinase 1 (RIPK1). <em>In vivo</em> pharmacokinetic studies were performed to determine the oral exposure of compound <strong>26</strong>. Finally, molecular docking elucidated that compound <strong>26</strong> could effectively bind to the allosteric pocket of RIPK1 and serve as a type III inhibitor. Taken together, our findings highlighted that compound <strong>26</strong> represented a promising lead compound for future necroptosis inhibitor development.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 7","pages":" 2514-2526"},"PeriodicalIF":3.597,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141506035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, and anticancer assessment of structural analogues of (E)-1-((3,4,5-trimethoxybenzylidene)amino)-4-(3,4,5-trimethoxyphenyl)imidazo[1,2-a]quinoxaline-2-carbonitrile (6b), an imidazo[1,2-a]quinoxaline-based non-covalent EGFR inhibitor†","authors":"Manvendra Kumar, Kiran T. Patil, Pritam Maity, Joydeep Chatterjee, Tashvinder Singh, Gaurav Joshi, Sandeep Singh and Raj Kumar","doi":"10.1039/D4MD00237G","DOIUrl":"10.1039/D4MD00237G","url":null,"abstract":"<p >In our quest to find improved anticancer therapeutics, we expedite the lead optimization of (<em>E</em>)-1-((3,4,5-trimethoxybenzylidene)amino)-4-(3,4,5-trimethoxyphenyl)imidazo[1,2-<em>a</em>]quinoxaline-2-carbonitrile (<strong>6b</strong>), an EGFR inhibitor previously discovered in our laboratory through an in-house screening program. The lead optimization was rationally initiated considering the catalytic site of EGFR. We synthesized twenty-nine new analogues of <strong>6b</strong> and assessed their anticancer activities. SAR studies highlighted the role of important groups in controlling anticancer activities. Among all, <strong>5a</strong> and <strong>5l</strong> were found to exhibit improved EGFR inhibition with anticancer asset potential. <em>In silico</em> studies corroborated with <em>in vitro</em> EGFR inhibitory results. The deeper analysis of <strong>5a</strong> and <strong>5l</strong> revealed that these synthetics could alter the MMP (Δ<em>Ψ</em><small>_m</small>) and significantly reduce the ROS levels in lung cancer cells. This is a vital prerequisite for better plausible EGFR inhibitors devoid of cardiotoxicity. qPCR analysis further revealed that the investigational compounds <strong>5a</strong> and <strong>5l</strong> were able to downregulate the expression of key oncogenes, <em>viz.</em>, KRAS, MAP2K, and EGFR. The downregulation of these genes suggests that the investigational compounds could interact and inhibit key players in the signalling cascade along with the EGFR, which may lead to the inhibition of the growth and prognosis of cancer cells <em>via</em> a holistic approach.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 7","pages":" 2322-2339"},"PeriodicalIF":3.597,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141523103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extension of multi-site analogue series with potent compounds using a bidirectional transformer-based chemical language model","authors":"Hengwei Chen, Atsushi Yoshimori and Jürgen Bajorath","doi":"10.1039/D4MD00423J","DOIUrl":"10.1039/D4MD00423J","url":null,"abstract":"<p >Generating potent compounds for evolving analogue series (AS) is a key challenge in medicinal chemistry. The versatility of chemical language models (CLMs) makes it possible to formulate this challenge as an off-the-beaten-path prediction task. In this work, we have devised a coding and tokenization scheme for evolving AS with multiple substitution sites (multi-site AS) and implemented a bidirectional transformer to predict new potent analogues for such series. Scientific foundations of this approach are discussed and, as a benchmark, the transformer model is compared to a recurrent neural network (RNN) for the prediction of analogues of AS with single substitution sites. Furthermore, the transformer is shown to successfully predict potent analogues with varying R-group combinations for multi-site AS having activity against many different targets. Prediction of R-group combinations for extending AS with potent compounds represents a novel approach for compound optimization.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 7","pages":" 2527-2537"},"PeriodicalIF":3.597,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141506036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive framework for managing metabolic dysfunction-associated steatotic liver disease: analyzing novel risk factors and advances in nanotechnology-based treatments and diagnosis","authors":"Lucia M. Chávez-López, Gabriela I. Carballo-López, Karina del Carmen Lugo-Ibarra and Ana B. Castro-Ceseña","doi":"10.1039/D4MD00420E","DOIUrl":"10.1039/D4MD00420E","url":null,"abstract":"<p >Metabolic dysfunction-associated steatotic liver disease (MASLD) presents a growing global health challenge requiring innovative approaches for effective management. This comprehensive review examines novel risk factors, including environmental pollutants like heavy metals, and underscores the complexity of personalized medicine tailored to individual patient profiles, influenced by gender and sex differences. Traditional treatments for MASLD, such as glucose- and lipid-lowering agents, show mixed results, highlighting the necessity for larger, long-term studies to establish safety and efficacy. Alternative therapies, including antioxidants, stem cells, and antiplatelets, although promising, demand extensive clinical trials for validation. This review highlights the importance of personalized medicine, considering individual variations and specific factors such as gender and sex, to optimize treatment responses. The shift from metabolic-associated fatty liver disease (MAFLD) to MASLD terminology underscores the metabolic components of the disease, aligning with the multiple-hit theory and highlighting the necessity for comprehensive risk factor management. Our vision advocates for an integrated approach to MASLD, encompassing extensive risk factor analysis and the development of safer, more effective treatments. Primary prevention and awareness initiatives are crucial in addressing the rising prevalence of MASLD. Future research must prioritize larger, long-term studies and personalized medicine principles to ensure the effective use of emerging therapies and technologies. The review underscores the need for continuous exploration and innovation, balancing the benefits and challenges of nanotechnology, to combat MASLD and improve patient outcomes comprehensively.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 8","pages":" 2622-2642"},"PeriodicalIF":3.597,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141531762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}