MedChemComm最新文献

{"title":"Designing halogen-free metal–phenolic imidazolium poly(ionic liquids) with multi-functional antibacterial, anti-inflammatory and cell proliferation properties for infected wounds","authors":"Danni Wang, Xiaodong He, Yingcui Cai, Chengju Sheng, Yuexiao Jia, Xiaojia Huang, Jia Ling Celestine Loh, Ruzhi Zhang, Mingmei Yang, Liqun Xu and Chao Zhou","doi":"10.1039/D5MD00612K","DOIUrl":"10.1039/D5MD00612K","url":null,"abstract":"<p >Infected wounds are challenging to heal because they are complicated by bacterial infections, persistent inflammation, and impaired cell proliferation. Recently, imidazolium poly(ionic liquids) (PILs), as highly effective antibacterial agents, have been developed for infected wound healing. However, traditional imidazolium-based PILs containing halogen groups have shown potential cytotoxicity. In this study, we designed halogen-free metal–phenolic imidazolium PILs (HMPIPs) with antibacterial, anti-inflammatory and cell proliferation properties. Firstly, poly(vinyl-butylimidazolium dihydroxyphenylpropionic acid) (PVD) was synthesized <em>via</em> radical polymerization, anion exchange, and catechol deprotection. Subsequently, the HMPIPs were individually coordinated with metals ions (Zn<small>²⁺</small>, Mg<small>²⁺</small>, Cu<small>²⁺</small>, and Fe<small>³⁺</small>). The results indicated that PVD@Zn could form stable MPIP microparticles. <em>In vitro</em> assays revealed that PVD@Zn exhibited potent antibacterial activity against <em>Escherichia coli</em> (MIC: 512 μg mL<small>⁻¹</small>) and <em>Staphylococcus aureus</em> (MIC: 128 μg mL<small>⁻¹</small>), likely due to the synergistic effects of the imidazolium group's positive charge. Additionally, PVD@Zn exhibited anti-inflammatory effects by suppressing reactive oxygen species (ROS) and nitric oxide (NO) levels, and downregulating TNF-α, IL-1β, IL-6, and iNOS through Zn<small>²⁺</small>-mediated regulation. Notably, it enhanced L929 fibroblast proliferation by 22% <em>via</em> upregulation of amino acid biosynthesis pathways. <em>In vivo</em> assays further demonstrated that PVD@Zn significantly accelerated wound closure (97% contraction within 11 days), effectively reduced bacterial load (93% eradication), and exhibited minimal systemic organ toxicity. The multifunctional HPIPs, PVD@Zn, demonstrated antibacterial, anti-inflammatory, and pro-proliferative properties, potentially reducing the risk of drug overuse during wound healing. This system holds promise for future clinical application as an encapsulated therapeutic agent.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 6031-6040"},"PeriodicalIF":3.597,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145432045","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":"Lactose-conjugated 2-iminothiazolidin-4-ones: synthesis, inhibitory activity and molecular simulations as potential inhibitors against enzymes responsible for type 2 diabetes","authors":"Hoang Thi Kim Van and Nguyen Dinh Thanh","doi":"10.1039/D5MD00538H","DOIUrl":"10.1039/D5MD00538H","url":null,"abstract":"<p >A series of new substituted lactose-conjugated 2-iminothiazolidin-4-ones <strong>7a–h</strong> were synthesized and scanned for their inhibitory activity against enzymes responsible for type 2 diabetes, including α-amylase, α-glucosidase, DPP-4, and PTP1B. Three lactose-conjugated 2-iminothiazolidin-4-ones <strong>7c</strong>, <strong>7e</strong>, and <strong>7f</strong> exhibited the highest inhibitory activity against the selected enzymes. Compounds <strong>7c</strong> and <strong>7e</strong> were the strongest inhibitors for DPP-4 and α-amylase, respectively, whereas <strong>7f</strong> exhibited strong inhibition against α-glucosidase and PTP1B. These compounds had also high anti-glycation and antioxidant activities and were not cytotoxic to the WI-38 cell line. A molecular docking study was applied to the three most potent inhibitors <strong>7c</strong>, <strong>7e</strong>, and <strong>7f</strong> in inhibition against enzymes 1OSE, 3TOP, 3W2T, and 1NNY. These ligands had active interactions with the residues in the catalytic pocket of these enzymes consistent with their inhibitory efficacy against each enzyme tested. Molecular dynamics simulations were applied for four typical complexes <strong>7e</strong>/1OSE, <strong>7f</strong>/3TOP, <strong>7c</strong>/3W2T, and <strong>7f</strong>/1NNY to validate the obtained <em>in vitro</em> data of these compounds. The obtained results indicated that these inhibitors had stable dynamic interactions in the catalytic pocket of the respective enzymes to promote their activity. The presence of the di-imine bridge bond helped to connect the thiazolidin-4-one ring and the aromatic ring, communicating the influence of the alternative groups on the overall activity of the target molecule. Additionally, the β-lactose portion contributes to the binding of the target molecule to the residue at the active site and increases the inhibitory activity of the target compounds.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 6132-6152"},"PeriodicalIF":3.597,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329781","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 of a highly potent bifunctional HIV-1 entry inhibitor targeting both gp120 and gp41","authors":"Xinmeng Du, Qing Li, Shu Du, Huan Wang, Anqi Shi, Ming Yuan, Fei Yu, Yang Liu and Chao Wang","doi":"10.1039/D5MD00603A","DOIUrl":"10.1039/D5MD00603A","url":null,"abstract":"<p >Previous studies have demonstrated the essential role of the envelope glycoprotein (Env) gp120 and gp41 N-terminal heptad repeat (NHR) region in human immunodeficiency virus type 1 (HIV-1) life cycle steps. Based on the multitarget-directed ligand (MTDL) design strategy, we herein report a series of bifunctional entry inhibitors consisting of an aroyl indoleoxoacetyl piperazine-based attachment inhibitor, IAC, and a gp41 NHR-targeting peptide fusion inhibitor SP22. We found that one of these chimeras, named ISP, showed potent inhibitory potency against HIV-1, about 180- and 54-fold over that of its parent inhibitors, IAC and SP22, respectively. Our work provides a potent peptide-based bifunctional HIV-1 entry inhibitor and offers new insights into the design of therapies against infection of other enveloped viruses.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 11","pages":" 5694-5701"},"PeriodicalIF":3.597,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233475","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":"Structure–activity relationships of fenarimol analogues with potent in vitro and in vivo activity against Madurella mycetomatis, the main causative agent of mycetoma","authors":"Hung Phat Duong, Dmitrij Melechov, Wilson Lim, Jingyi Ma, Kymberley R. Scroggie, Luxsika Rajendra, Benjamin Perry, Luiza R. Cruz, Rahman Shah Zaib Saleem, Peter J. Rutledge, Alice Motion, Wendy W. J. van de Sande and Matthew H. Todd","doi":"10.1039/D5MD00427F","DOIUrl":"10.1039/D5MD00427F","url":null,"abstract":"<p >The fenarimol analogue EPL-BS1246 was previously discovered to be potent against <em>Madurella mycetomatis</em>, the causative agent of the neglected tropical disease mycetoma. Further evaluation of a small set of fenarimol analogues <em>in vivo</em> revealed a correlation between efficacy and the lipophilicity (log <em>D</em>) of the analogues. To explore both this correlation and the series structure–activity relationship (SAR), we have evaluated a total of 185 fenarimol analogues derived from five different daughter chemotypes. Potent (MIC<small>₅₀</small> &lt; 9 μM) <em>in vitro</em> activity was found for 22 analogues, five of which gave promising results in an <em>in vivo</em> larval survival assay. Again, a trend towards prolonged larval survival (better <em>in vivo</em> activity) was noted in analogues with log <em>D</em> values &lt;2.5. Insights into the SAR could be gleaned that suggested optimal substituents for the rings forming the fenarimol core.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 6094-6108"},"PeriodicalIF":3.597,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12529582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329813","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":"Investigation of the multifunctional profile of dihydroquinazoline derivatives as potential therapeutics for Alzheimer's disease","authors":"Kailash Jangid, Bharti Devi, Ruby Dahiya, Jayapriya Mishra, Vinay Kumar, Jasvinder Singh Bhatti, Suresh Thareja and Vinod Kumar","doi":"10.1039/D5MD00626K","DOIUrl":"10.1039/D5MD00626K","url":null,"abstract":"<p >Multitarget directed ligands represent an innovative strategy in the management of Alzheimer's disease (AD) by addressing its multifactorial etiology. These agents are designed to simultaneously modulate multiple key targets involved in the disease progression, offering a holistic approach for the effective treatment of AD. The current work presents the synthesis and evaluation of novel dihydroquinazoline-based multitargeting agents for the management of Alzheimer's disease. Most of the compounds showed good selectivity for AChE and MAO-B, and two compounds, <em>viz.</em><strong>K2V-9</strong> and <strong>K2V-12</strong>, emerged as potent inhibitors against both the targets. Compound <strong>K2V-9</strong> displayed IC<small>₅₀</small> values of <strong>1.72 ± 0.01 μM</strong> and <strong>0.950 ± 0.52 μM</strong> against AChE and MAO-B, respectively. Compound <strong>K2V-12</strong> showed IC<small>₅₀</small> values of <strong>1.10 ± 0.078 μM</strong> and <strong>1.68 ± 0.25 μM</strong> against AChE and MAO-B, respectively. Moreover, amyloid β self-aggregation inhibition studies were performed, where <strong>K2V-9</strong> and <strong>K2V-12</strong> showed percentage inhibitions of 37.34% and 48.10%, respectively, after 48 h. Both compounds were found to be non-toxic and neuroprotective and showed the capability of reducing the ROS levels in SHSY-5Y cells. Reversibility and kinetic studies of these lead compounds showed that both molecules produced reversible and mixed-type of inhibition against the targeted enzymes. In the docking and molecular dynamics simulation studies, <strong>K2V-9</strong> and <strong>K2V-12</strong> were found to be well accommodated in the active cavity with good thermodynamic stability.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 6153-6172"},"PeriodicalIF":3.597,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145346904","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":"Recent advances in triazole hybrid molecules for the therapeutic management of neglected tropical diseases","authors":"Jatin Malik, Gauri Karande, Sankaranarayanan Murugesan and Kondapalli Venkata Gowri Chandra Sekhar","doi":"10.1039/D5MD00572H","DOIUrl":"10.1039/D5MD00572H","url":null,"abstract":"<p >The triazole scaffold has garnered considerable attention over the preceding decade as a privileged pharmacophore in the rational design of chemotherapeutic agents targeting neglected tropical diseases (NTDs). This review provides a comprehensive elucidation of the multifaceted research dedicated to the structural optimization of the triazole nucleus and its consequential outcomes on biological efficacy. Emphasis is placed on the methodical investigation of diverse substituents appended to the triazole core, underscoring the profound influence of seemingly marginal modifications on critical pharmacological parameters. Through a comprehensive deconstruction of structure–activity relationships (SAR), this exposition identifies the essential functional moieties underpinning biological efficacy that potentiate anti-parasitic, anti-fungal, and anti-viral activities across a spectrum of NTD-relevant biological targets. These insights deepen the knowledge of triazole based hybrid molecules and guide future rational design of novel compounds. By synthesizing and analyzing findings from a wide array of studies, this review aims to serve as a valuable resource for researchers interested in the continued development of triazole derivatives to manage neglected tropical diseases effectively.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 11","pages":" 5292-5317"},"PeriodicalIF":3.597,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233454","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 biological evaluation of indazole-based PLK4 inhibitors","authors":"Cunzheng Fan, Nian Liu, Ningyuan Hu, Minghui Tong, Xuan Shi, Han Wang, Wenqiang Sun, Zehui Qi, Haoyu Zhang, Yixiang Sun, Zixuan Gao, Dongmei Zhao and Maosheng Cheng","doi":"10.1039/D5MD00654F","DOIUrl":"10.1039/D5MD00654F","url":null,"abstract":"<p >Polo-like kinase 4 (PLK4), a member of the serine/threonine protein kinase family, serves as a central regulator of centriole duplication and plays a critical role in eukaryotic mitosis. Overexpression of PLK4 in several cancer types underscores its potential as a therapeutic target. In our previous studies, compound <strong>28t</strong> demonstrated acceptable kinase inhibitory activity but exhibited poor cellular activity. Consequently, <strong>28t</strong> was selected as a lead compound for further optimization. Through functional group migration and rational drug design strategies, we conducted structural modifications that ultimately yielded 23 novel indazole-based PLK4 inhibitors. Among these, compound <strong>C05</strong> exhibited exceptional kinase inhibitory activity (IC<small>₅₀</small> &lt; 0.1 nM). At the cellular level, <strong>C05</strong> demonstrated potent antiproliferative effects against IMR-32 (neuroblastoma), MCF-7 (breast cancer), and H460 (non-small cell lung cancer) cell lines, with IC<small>₅₀</small> values of 0.948 μM, 0.979 μM, and 1.679 μM, respectively. Notably, compound <strong>C05</strong> demonstrated favorable kinase selectivity towards PLK4 among the 10 kinases tested, achieving an inhibition rate of 87.45%. Further pharmacological experimental studies, including apoptosis induction, cell cycle arrest analysis, and clonogenic formation experiments, revealed that <strong>C05</strong> outperformed the positive control <strong>LCR-263</strong> in both potency and efficacy. Western blot analysis demonstrated that compound <strong>C05</strong> effectively suppressed PLK4 autophosphorylation at 4 μM. Unfortunately, compound <strong>C05</strong> demonstrated poor metabolic stability in human liver microsomes (HLMs), exhibiting a short half-life (<em>T</em><small>_1/2</small>) of 2.69 minutes under standard incubation conditions. Notwithstanding the suboptimal metabolic stability, the compelling biological activity profile of compound <strong>C05</strong> warrants further structural refinement.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 11","pages":" 5717-5735"},"PeriodicalIF":3.597,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245017","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":"The rise of ultrashort cationic β-peptides as promising antimicrobial therapeutics","authors":"Hadiya Amin Kantroo, Itibaw Farooq and Zahoor Ahmad","doi":"10.1039/D5MD00596E","DOIUrl":"10.1039/D5MD00596E","url":null,"abstract":"<p >Antimicrobial resistance (AMR) is a mounting global health crisis demanding novel, sustainable therapeutic strategies beyond traditional antibiotics. Ultra-short cationic β-peptides have emerged as a promising class of synthetic antimicrobial foldamers with broad-spectrum activity, remarkable proteolytic stability, and low resistance potential. Designed through rational approaches, these 2–10 residue peptides leverage amphipathicity, structural rigidity, and electrostatic interactions to disrupt microbial membranes, biofilms, and even intracellular pathogens. Notably, they exhibit synergistic effects with conventional antibiotics and minimal toxicity to mammalian cells. Emerging <em>in vivo</em> studies in murine models further suggest that ultra-short β-peptides can reduce pathogen burden and improve survival, although the available data remain limited and warrant careful interpretation. This review provides a comprehensive overview of their design, mechanism of action, antimicrobial spectrum, including bacteria, fungi, viruses, and protozoa, and relevance to One Health frameworks. Key translational bottlenecks, including delivery challenges, immunogenicity, pharmacokinetics, and regulatory hurdles, are critically assessed. We also identify major research gaps and propose future directions to fully harness the therapeutic potential of ultra-short β-peptides against multidrug-resistant infections.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 11","pages":" 5235-5254"},"PeriodicalIF":3.597,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131914","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 biological evaluation of 2-phenylthiazole CYP51 inhibitors","authors":"Kejian Li, Guoqi Zhang, Wenzhan Hao, Jinming Liu, Yixiang Sun, Zixuan Gao, Zirui Luo, Rui Liu, Nian Liu, Haoyu Zhang, Xudong Wu, Dongmei Zhao and Maosheng Cheng","doi":"10.1039/D5MD00535C","DOIUrl":"10.1039/D5MD00535C","url":null,"abstract":"<p >Fungal pathogens have emerged as one of the most significant threats to global public health. Invasive fungal infections, characterized by high morbidity and mortality rates, have become one of the most severe diseases, posing a substantial threat to human health. In this study, a rational drug design strategy was employed, targeting lanosterol 14α-demethylase (CYP51). Using <strong>SCZ-14</strong>, a CYP51 inhibitor with moderate antifungal activity, as the lead compound, 27 novel 2-phenylthiazole derivatives were designed and synthesized through two rounds of structural optimization. Among these compounds, compound <strong>B9</strong> exhibited potent inhibitory activity against seven common clinically susceptible fungal strains and moderate activity against six fluconazole-resistant fungi strains, and it demonstrated low cytotoxicity. In addition, the preferred compound <strong>B9</strong> had good drug-like properties according to the prediction software. In addition, molecular dynamics studies were conducted on compound <strong>B9</strong>. All the results of the above research show that the target compound <strong>B9</strong> is valuable for further study.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 6173-6189"},"PeriodicalIF":3.597,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145346915","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 4-substituted phenylpyrazolidinone derivatives as potent Ku70/80 targeted DNA-PK inhibitors","authors":"Narva Deshwar Kushwaha, Pamela VanderVere-Carozza, Tyler L. Vernon, Pamela L. Mendoza-Munoz, Jitender D. Gaddameedi, Karim Ben Ali Gacem, Joseph Engel, Jean-Baptiste Charbonnier, Navnath S. Gavande and John J. Turchi","doi":"10.1039/D5MD00263J","DOIUrl":"10.1039/D5MD00263J","url":null,"abstract":"<p >The Ku70–Ku80 (Ku) heterodimer complex plays a central role in the non-homologous end joining (NHEJ) double-strand break (DSB) repair pathway and the DNA damage response (DDR). Like DNA–PK, Ku is a promising drug target for cancer treatment when combined with radiotherapy or DSB-inducing agents. We have previously reported the first-in-class, early-generation, highly potent, and specific Ku–DNA binding inhibitors (Ku-DBi's) that block the Ku interaction with DNA and inhibit DNA-PK kinase activity. These early-generation Ku-DBi's also inhibit cellular DNA-PK, NHEJ-catalyzed DSB repair, sensitize non-small cell lung cancer (NSCLC) cells to DSB-inducing agents, and potentiate the cellular effects of these agents <em>via</em> p53 phosphorylation through the activation of the ATM pathway. In this study, we report a comprehensive structure–activity relationship (SAR) analysis around the initial <strong>X80</strong> hit molecule to develop highly potent Ku-DBi's. Early generation Ku-DBi's display a potent Ku–DNA binding inhibitory activity with a range of 2 to 6 μM, and DNA-PK inhibitory activity in the nanomolar range of approximately 110 nM. Microscale thermophoresis assay shows that these compounds inhibit Ku70–Ku80 binding to DNA with a Kd value of 0.4–6.4 μM. The thermal stability analysis also supports the notion that these Ku-DBi's bind to the Ku as measured by nanoDSF (Differential Scanning Fluorimetry), which is consistent with the observed SAR trends. These Ku-DBi's may serve as candidate compounds for further modification and development as anticancer therapeutics in combination with radiotherapy or DSB-inducing agents to treat certain DNA repair-deficient cancers.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 11","pages":" 5534-5561"},"PeriodicalIF":3.597,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131896","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}