Drug Development Research最新文献

{"title":"Linear Antimicrobial Peptide, Containing a Diindolyl Methane Unnatural Amino Acid, Potentiates Gentamicin Against Methicillin-Resistant Staphylococcus aureus","authors":"Shalini Singh,&nbsp;Grace Kaul,&nbsp;Manjulika Shukla,&nbsp;Abdul Akhir,&nbsp;Shubhandra Tripathi,&nbsp;Abhinav Gupta,&nbsp;Rakhi Bormon,&nbsp;Nisanth N. Nair,&nbsp;Sidharth Chopra,&nbsp;Sandeep Verma","doi":"10.1002/ddr.70070","DOIUrl":"https://doi.org/10.1002/ddr.70070","url":null,"abstract":"<div>\u0000 \u0000 <p>The headway for the management of emerging resistant microbial strains has become a demanding task. Over the years, antimicrobial peptides (AMP), have been recognized and explored for their highly systematized SAR and antibacterial properties. With this background, we have reported a new class of AMPs. These peptides incorporate an unnatural amino acid, with a motivation from cruciferous bioactive phytochemical bisindoles methane derivatives with highly selective antimicrobial action. These peptides may also be considered as linear derivatives of hirsutide isolated from entomopathogenic fungus. The synthesized peptides were tested for their antimicrobial activity against an ESKAPE pathogen panel, where peptide <b>3</b> exhibited equipotent MIC and potent synergistic action along with gentamicin against <i>Staphylococcus aureus</i> and <i>Enterococcus</i> clinical isolates. This combination was also able to repotentiate gentamicin against NRS119, a gentamicin-resistant MRSA. Molecular dynamics study and free energy calculations provided insights to membrane disruptive properties of AMP action, which assisted gentamicin pass through the lipid–water interface.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional Docetaxel Cholesterol-Polyethylene Glycol Co-Modified Poly (N-Butyl) Cyanoacrylate Nanoparticles for Brain Tumor Therapy","authors":"Xiao Hu,&nbsp;Feifei Yang,&nbsp;Yonghong Liao,&nbsp;Lin Li,&nbsp;Lan Zhang","doi":"10.1002/ddr.70069","DOIUrl":"https://doi.org/10.1002/ddr.70069","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Owing to the presence of the blood-brain barrier and the lack of significant specificity towards tumor cells after entry into the brain, the unsuccessful delivery of anticancer drugs to the treatment of brain tumors. The hypothesis that cholesterol-PEG co-modified poly (N-butyl) cyanoacrylate nanoparticles (CLS-PEG NPs) are an effective carrier for the treatment of brain tumors was verified, and the mechanism of its treatment for brain tumors was preliminarily explored. In this study, we used multifunctional poly (N-butyl) cyanoacrylate nanoparticles modified with cholesterol and polyethylene glycol (PEG) as a drug delivery system to encapsulate the anticancer drug docetaxel (DTX). Cell anti-proliferation tests showed that CLS-PEG NPs increased the inhibitory effect of DTX. A pharmacokinetic study indicated that CLS-PEG NPs achieved sustained release for 8 h. These experimental results demonstrated that CLS-PEG NPs amplified the concentration of the drug transported to the brain and sustained drug release in the brain. In addition, CLS-PEG NPs led to better pharmacological efficacy in an orthotopic brain glioma rat model. The survival rate of rats in the CLS-PEG NPs group was significantly prolonged to 28 d. We also found that CLS-PEG NPs inhibited M2 microglial polarization. These results indicate that CLS-PEG NPs are a prospective drug delivery system for targeting brain tumors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Pyrrolone-Fused Benzosuberene MK2 Inhibitors as Promising Therapeutic Agents for HNSCC: In Vitro Efficacy, In-Vivo Safety, and Pharmacokinetic Profiling","authors":"Prince Anand,&nbsp;Jyoti Chhimwal,&nbsp;Sumit Dhiman,&nbsp; Yamini,&nbsp;Vikram Patial,&nbsp;Pralay Das,&nbsp;Zabeer Ahmed,&nbsp;Utpal Nandi,&nbsp;Mahvash Tavassoli,&nbsp;Yogendra Padwad","doi":"10.1002/ddr.70062","DOIUrl":"https://doi.org/10.1002/ddr.70062","url":null,"abstract":"<div>\u0000 \u0000 <p>MAPKAPK2/MK2 is well implicated in the progression of Head and Neck Squamous Cell Carcinoma (HNSCC), and potent MK2-inhibitors are required to suppress its activity. Several MK2-inhibitors have been developed in recent years to combat its effects on cancer. However, inadequate solubility, insufficient cellular permeability, systemic toxicity-mediated side effects, and low bioavailability have severely impeded the advancement of MK2-inhibitors to clinical trials. This void necessitates research to develop less toxic and more bioavailable potent MK2-inhibitors in HNSCC. In the present article, we have evaluated the in-vitro efficacy, in-vivo single-dose acute toxicity, and in-vivo pharmacokinetic profiling of recently developed PfBS (pyrrolone-fused benzosuberene) MK2-inhibitor analogues against HNSCC. The PfBS MK2 inhibitor analogues impeded HPV+ and HPV- HNSCC cell proliferation and two-dimensional migration. Moreover, MK2-inhibitors lowered HNSCC cell clonogenic survival in a dose-dependent manner, significantly enhancing radiation-induced cell death via exerting radio-sensitization effects. Furthermore, γ-H2AX immunostaining revealed that PfBS analogues impaired DNA damage repair in HNSCC cells exposed to gamma radiation. In mice, PfBS MK2 inhibitors at 300 mg/kg were well-tolerated without any lethal effects. Pharmacokinetic studies showed that PfBS analogues exhibited rapid absorption (Tmax), adequate plasma concentration above the micromolar level (C0 or Cmax), limited tissue distribution (Vd), and faster elimination from the body (Cl). Overall, this study summarizes in-vitro efficacy, safety, and pharmacokinetics of developed MK2-inhibitors and opens doors for pharmacodynamics and mechanism of action study of most effective leads in HNSCC.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Amyloid A1 Mediates Paclitaxel Resistance via MD2-Dependent Pathways in Triple-Negative Breast Cancer","authors":"Kangmin Chen,&nbsp;Yanni Zhao,&nbsp;Tianyang Jin,&nbsp;Tingxin Xu,&nbsp;Conglun Zhu,&nbsp;Hui Shen,&nbsp;Xiaohong Xu,&nbsp;Yongsheng Jiang,&nbsp;Yi Wang,&nbsp;Shihang Xue","doi":"10.1002/ddr.70047","DOIUrl":"https://doi.org/10.1002/ddr.70047","url":null,"abstract":"<div>\u0000 \u0000 <p>Triple-negative breast cancer (TNBC) is difficult to treat due to the lack of clear therapeutic targets. Paclitaxel (PTX) is commonly used to treat TNBC, but drug resistance limits its effectiveness. Myeloid differentiation protein 2 (MD2) and serum amyloid A1 (SAA1) are involved in various diseases, including infections, inflammatory diseases, and cancer. We investigated their role in PTX resistance to identify potential anti-TNBC drugs. In this study, we investigated the changes of SAA1 in TNBC tissues and its role in PTX-induced TNBC cells. Our study revealed SAA1 expressed in the human TNBC subtype and TNBC cells. PTX and CIS induce SAA1 in TNBC cells, and PTX induces inflammatory response via SAA1 in TNBC cells. MD2 blockade increased the sensitivity of TNBC cells to PTX, which was related to the expression of SAA1 during PTX-caused damage of TNBC cells. In further research, SAA1 binds to MD2, promotes the combination of TLR4/MD2 and TLR4/MyD88, activates the NF-κB signaling pathway, and creates the inflammatory microenvironment for cancer cells. Our study reports for the first time that the PTX/SAA1/MD2 axis exists in the PTX-resistance process, which could be a potential treatment target of PTX-resistance.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside CK Promotes Cell Apoptosis via Regulating P53 Signal Pathway in Non-Small Cell Lung Cancer","authors":"Xinze Liu,&nbsp;Lin Feng,&nbsp;Xin Jin,&nbsp;Kaijing Sun,&nbsp;Ying Sun,&nbsp;Xinmin Wu,&nbsp;Mingjie Xia,&nbsp;Renbo Tan,&nbsp;Hongmei Yang,&nbsp;Guangzhe Li,&nbsp;Wei Wu,&nbsp;Shuang Zu,&nbsp;Anning Li,&nbsp;Changbao Chen,&nbsp;Xilin Wan","doi":"10.1002/ddr.70050","DOIUrl":"https://doi.org/10.1002/ddr.70050","url":null,"abstract":"<div>\u0000 \u0000 <p>Non-small cell lung cancer (NSCLC) is a malignant tumor with high morbidity and mortality. Ginsenosides have been shown to have strong antitumor activity, inhibiting tumor cell growth and promoting apoptosis. In this paper, the effects of ginsenoside CK on the proliferation and apoptosis of NSCLC 95D and NCI-H460 cells were investigated by CCK8, colony formation assay, flow cytometry, fluorescence staining assay, and Western Blot, and it was found that ginsenoside CK could significantly inhibit the growth and proliferation of non-small cell lung cancer, and it was also clarified that the mechanism of its action was realized by the mitochondrial apoptosis pathway. It provides new therapeutic ideas for lung cancer and other major tumor diseases.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Chlorophenyl Dioxo-Imidazolidines for Bacterial Biofilm","authors":"Shanmugha Samy,&nbsp;Manikandan Alagumuthu,&nbsp;Ooha Dharani Yalamaddi,&nbsp;Milind Shrinivas Dangate","doi":"10.1002/ddr.70054","DOIUrl":"https://doi.org/10.1002/ddr.70054","url":null,"abstract":"<div>\u0000 \u0000 <p>Biofilm is a “growing” problem and needs effective remedial agents. Here we report novel methyl 4-((4-(4-chlorophenyl)-2,5-dioxoimidazolidin-1-yl) methyl) benzoate derivatives (<b>5a-l</b>) as antibiofilm and antimicrobial agents evaluated with both in silico and in vitro techniques. When it comes to Gram-positive bacterial strains like <i>Staphylococcus aureus</i> (MTCC 737), MRSA and <i>Streptococcus pneumoniae</i> (MTCC 1936), and Gram-negative bacterial strains like <i>Pseudomonas aeruginosa</i> (MTCC 424) and <i>Escherichia coli</i> (MTCC 443), the minimum inhibitory concentration (MIC), minimum biofilm inhibition concentration (MBIC), and anti-biofilm activity were measured. Out of all the compounds (<b>5a-l</b>), <b>5b</b> and <b>5d</b> showed no toxicity to mammalian cells and were equally active against various Gram-positive and Gram-negative bacteria at low concentrations (MIC: 0.1–9.5 µg/mL). Compounds <b>5b</b> and <b>5d</b> were also validated for the DNA gyrase inhibition potential as an antimicrobial mechanism of action in vitro. These compounds showed high level DNA gyrase inhibition potentials (IC₅₀ 0.025 µM, ≥ 98 relative % activity and 0.24 µM, ≥ 94 relative % activity respectively. In the end, we have identified <b>5b</b> and <b>5d</b> as most effective among <b>5a-l</b> and are considered for further preclinical studies.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal ALKBH5 Alleviates Vascular Calcification by Suppressing Cell Apoptosis via m6A-Modified GSDME","authors":"Guian Xu,&nbsp;Qingman Li,&nbsp;Lijie Zhu,&nbsp;Tingjie Yang,&nbsp;Yapan Yang,&nbsp;Honghui Yang","doi":"10.1002/ddr.70065","DOIUrl":"https://doi.org/10.1002/ddr.70065","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to explore the function and regulatory mechanism of ALKBH5 in the progression of coronary artery calcification. Human aortic vascular smooth muscle cells (HA-VSMCs) were treated with inorganic phosphate (Pi) and exosomes derived from bone marrow mesenchymal stem cell (BMSC) carrying ALKBH5, a GSDME overexpression vector or si-GSDME. The morphology and size of the exosomes were assessed using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Calcium deposition was measured using Alizarin red staining and cell pyroptosis was evaluated using Hoechst 33342/PI staining. The association between ALKBH5 and m6A modifications was confirmed by methylated-RNA immunoprecipitation assay (MeRIP) and dot blot assays. The expression levels of ALKBH5 and GSDME were quantified by quantitative real-time polymerase chain reaction (qRT-PCR), and protein levels were quantified by western blot. BMSCs-derived exosomes reduced calcium deposition and cell pyroptosis in Pi-treated HA-VSMCs. Exosomes containing ALKBH5 overexpression inhibited high mobility group box 1 (HMGB1) and cell apoptosis, thereby promoting vascular calcification, whereas ALKBH5 knockdown in exosomes exerted the opposite effect on calcification development. Additionally, ALKBH5 was found to regulate the m6A modification of GSDME. Overexpression of GSDME reversed the effects of ALKBH5 in exosomes on HMGB1 expression and cell apoptosis. Exosomal ALKBH5 mitigated HMGB1 expression and cell pyroptosis by modulating the m6A modification of GSDME, thus influencing the progression of coronary artery calcification.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro and In Silico Assessment of Antileishmanial Potential of Novel Tri- and Penta-Valent Antimony Complexes With Phenolic Ligands","authors":"Syeda Aaliya Shehzadi,&nbsp;Faiz Ahmed,&nbsp;Arshad Islam,&nbsp;Zeshan Ahmed,&nbsp;Khizar Abdullah,&nbsp;Farhan Younas,&nbsp;Ali Haider,&nbsp;Muhammad Tariq,&nbsp;Ahmed Noureldeen,&nbsp;Bander Albogami,&nbsp;Hadeer Darwish,&nbsp;Fatemah Enad M. Alajmi","doi":"10.1002/ddr.70067","DOIUrl":"https://doi.org/10.1002/ddr.70067","url":null,"abstract":"<div>\u0000 \u0000 <p>Leishmaniasis, caused by protozoan parasites of the genus <i>Leishmania</i>, affects nearly 12 million people annually worldwide, and has limited, highly toxic therapeutic options. This study reports the synthesis, in vitro and in silico evaluations of four novel antimony complexes (<b>3a-3d</b>) as potent and safe antileishmanial agents. The complexes were synthesized using Sb-salts with different phenolic ligands and characterized by elemental analysis, FT-IR and NMR spectroscopic techniques. Structural parameters were further evaluated via DFT studies. The antileishmanial activity of these complexes (<b>3a-3d</b>) was assessed in vitro against promastigote and axenic amastigote forms of <i>Leishmania tropica</i>, showing promising potential as antileishmanial agents. Complex <b>3a</b> and <b>3c</b> were particularly active, with IC₅₀ values of 10.8 ± 2.1 and 11.0 ± 2.0 μmol/L against promastigotes, and 20.14 ± 6.11 and 27.72 ± 0.13 μmol/L against amastigotes, respectively. Molecular docking analysis against receptor protein (PDB ID: 8FI6) from genus <i>Leishmania</i> revealed high binding conformations of synthesized molecules within the active cavity of the target protein. With the lowest Ki value of 1.25 and a pattern of hydrophobic π-interactions and strong conventional hydrogen bonds, complex <b>3d</b> demonstrated excellent binding affinities within the active pocket. Notably, these complexes exhibited low cytotoxicity, compared to the standard antileishmanial drugs, TA (potassium antimonyl tartrate) and AmB (Amphotericin B), with hemolysis rates of &lt; 12% for all complexes. Our findings suggest that these complexes (<b>3a-3d</b>) are promising candidates for the development of new, safer antileishmanial therapies, combining potent activity against <i>L. tropica</i> with significantly lower cytotoxicity compared to existing treatments.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Curcumin's Molecular Targets and Its Potential in Suppressing Skin Inflammation Using Network Pharmacology and In Vitro Studies","authors":"Anjana Sureshbabu,&nbsp;Elena Smirnova,&nbsp;Do Thi Cat Tuong,&nbsp;Sangeetha Vinod,&nbsp;Sungyeon Chin,&nbsp;Mohammad Moniruzzaman,&nbsp;Kalaiselvi Senthil,&nbsp;Dong I. Lee,&nbsp;Karthikeyan Adhimoolam,&nbsp;Taesun Min","doi":"10.1002/ddr.70058","DOIUrl":"https://doi.org/10.1002/ddr.70058","url":null,"abstract":"<div>\u0000 \u0000 <p>Curcumin, a polyphenol compound derived from turmeric, has garnered attention for its anti-inflammatory and antioxidant properties, making it a promising candidate for treating skin inflammation. Despite its potential, the underlying pharmacological effects to skin inflammation remain unclear. Therefore, this study aimed to reveal the curcumin's molecular targets and its potential in suppressing skin inflammation using network pharmacology and in vitro experiments. A total of 7,393 and 239 targets related to curcumin and skin inflammation, respectively, were obtained from public databases. By drawing a Venn diagram, 216 common targets were identified as candidate targets. These targets were subjected to gene function and pathway enrichment analyses, and a protein-protein interaction network was established to investigate curcumin's impact on inflammation. The gene functions were mainly associated with inflammatory response, membrane raft, and serine-type endopeptidase activity. The NF-κB and MAPK pathways could be the major pathways through which curcumin acts on skin inflammation. Ten major targets of curcumin in the treatment of skin inflammation were identified: AKT1, TNF, EGFR, APP, MMP9, STAT3, HIF1A, PTGS2, EP300, and GSK3B. Molecular docking analysis results showed high binding affinity of curcumin to PTGS2, GSK3B, HIF1A, and STAT3, which may contribute to its inhibitory effect on skin inflammation. In vitro experiments confirmed curcumin's anti-inflammatory effect on inflammation by reducing the expression levels of NO, IL-1β, and IL-6 in LPS-induced HaCaT cells. Taken together, this study reveals major targets and pathways of curcumin in the treatment of skin inflammation, paving the way for invivo and clinical investigations.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reviewing on AI-Designed Antibiotic Targeting Drug-Resistant Superbugs by Emphasizing Mechanisms of Action","authors":"Zafer Yönden,&nbsp;Samira Reshadi,&nbsp;Ahmad Farrokh Hayati,&nbsp;Mohammad Hossein Hooshiar,&nbsp;Sholeh Ghasemi,&nbsp;Hakan Yönden,&nbsp;Amin Daemi","doi":"10.1002/ddr.70066","DOIUrl":"https://doi.org/10.1002/ddr.70066","url":null,"abstract":"<div>\u0000 \u0000 <p>The emergence of drug-resistant bacteria, often referred to as “superbugs,” poses a profound and escalating challenge to global health systems, surpassing the capabilities of traditional antibiotic discovery methods. As resistance mechanisms evolve rapidly, the need for innovative solutions has never been more critical. This review delves into the transformative role of AI-driven methodologies in antibiotic development, particularly in targeting drug-resistant bacterial strains (DRSBs), with an emphasis on understanding their mechanisms of action. AI algorithms have revolutionized the antibiotic discovery process by efficiently collecting, analyzing, and modeling complex datasets to predict both the effectiveness of potential antibiotics and the mechanisms of bacterial resistance. These computational advancements enable researchers to identify promising antibiotic candidates with unique mechanisms that effectively bypass conventional resistance pathways. By specifically targeting critical bacterial processes or disrupting essential cellular components, these AI-designed antibiotics offer robust solutions for combating even the most resilient bacterial strains. The application of AI in antibiotic design represents a paradigm shift, enabling the rapid and precise identification of novel compounds with tailored mechanisms of action. This approach not only accelerates the drug development timeline but also enhances the precision of targeting superbugs, significantly improving therapeutic outcomes. Furthermore, understanding the underlying mechanisms of these AI-designed antibiotics is crucial for optimizing their clinical efficacy and devising proactive strategies to prevent the emergence of further resistance. AI-driven antibiotic discovery is poised to play a pivotal role in the global fight against antimicrobial resistance. By leveraging the power of artificial intelligence, researchers are opening new frontiers in the development of effective treatments, ensuring a proactive and sustainable response to the growing threat of drug-resistant bacteria.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}