Molecular Diversity最新文献_第5页

Phytochemical targeting of SASP2-mediated DNA protection to impair spore resilience in Bacillus cereus: A Computational Investigation. 植物化学靶向sasp2介导的DNA保护损害蜡样芽孢杆菌孢子弹性：一项计算研究。

IF 4.3 2区化学

Molecular Diversity Pub Date : 2026-10-01 Epub Date: 2026-05-03 DOI: 10.1007/s11030-026-11538-x

Rajaram Abhirami, Chandrabose Selvaraj, Sanjeev Kumar Singh

{"title":"Phytochemical targeting of SASP2-mediated DNA protection to impair spore resilience in Bacillus cereus: A Computational Investigation.","authors":"Rajaram Abhirami, Chandrabose Selvaraj, Sanjeev Kumar Singh","doi":"10.1007/s11030-026-11538-x","DOIUrl":"10.1007/s11030-026-11538-x","url":null,"abstract":"Spore-forming bacteria such as Bacillus cereus pose a significant public health challenge due to their ability to survive harsh environmental conditions, resist conventional decontamination strategies, and cause recurrent infections in clinical and food-associated environments. This persistence is primarily associated with sporulation, a tightly regulated developmental process in which long-term survival depends on maintaining genome integrity while cellular metabolism remains largely inactive. DNA-binding proteins are therefore central to sporulation, as effective DNA condensation and protection are essential for sporulation progression and cyst wall maturation. Among these, α/β-class small acid-soluble proteins (SASPs), particularly SASP2, bind to the DNA minor groove and stabilize the genome during dormancy. In this study, a structural model of the B. cereus SASP2-DNA complex was constructed and analyzed through an integrated computational approach to identify compounds targeting this interaction. Phytochemicals derived from Garcinia mangostana, Garcinia cowa, Ficus exasperata, and Entada abyssinica, previously reported for antimicrobial activity, were evaluated for their potential to interact with the SASP2-DNA interface, a mechanism not previously explored. Several compounds showed strong binding affinity at the SASP2-DNA minor-groove interface and were predicted to influence key interactions under simulated stress conditions, leading to DNA compaction stability and stress tolerance, which may subsequently affect cyst wall formation and spore viability. Notably, the identification of plant-derived compounds capable of targeting the SASP2-DNA interface represents a novel observation. Overall, these findings provide a promising computational basis for exploring strategies to limit the persistence and transmission of B. cereus infections.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"8135-8159"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure-guided design and synthesis of Etoricoxib analogues for selective COX-2 inhibition: in vitro assessment and computational insights with prospective in vivo confirmation. 结构导向设计和合成依托昔布类似物选择性抑制COX-2：体外评估和计算见解与前瞻性体内确认。

IF 4.3 2区化学

Molecular Diversity Pub Date : 2026-10-01 Epub Date: 2026-05-09 DOI: 10.1007/s11030-026-11555-w

Mohammed H Alqarni, Mohamed K Elgohary, Mahmoud Abdelrahman Alkabbani, Ahmed I Foudah, Aftab Alam, Tariq M Aljarba, Hatem A Abdel-Aziz, Mahmoud S Elkotamy

{"title":"Structure-guided design and synthesis of Etoricoxib analogues for selective COX-2 inhibition: in vitro assessment and computational insights with prospective in vivo confirmation.","authors":"Mohammed H Alqarni, Mohamed K Elgohary, Mahmoud Abdelrahman Alkabbani, Ahmed I Foudah, Aftab Alam, Tariq M Aljarba, Hatem A Abdel-Aziz, Mahmoud S Elkotamy","doi":"10.1007/s11030-026-11555-w","DOIUrl":"10.1007/s11030-026-11555-w","url":null,"abstract":"The selective inhibition of cyclooxygenase-2 (COX-2) is an effective approach for managing inflammatory disorders; however, safety concerns related to current coxibs highlight the need for better alternatives. This study presents the rational design, synthesis, and evaluation of a series of novel etoricoxib-inspired pyridine-based derivatives as potential selective COX-2 inhibitors. Systematic exploration of structure-guided modifications, including heterocyclic scaffold hybridization, pyridine attachment position, and aryl substitution, was conducted to clarify structure-activity relationships. In vitro enzymatic assays demonstrated that multiple compounds displayed significant COX-2 inhibition with advantageous selectivity indices over COX-1, notably compounds 8e, 8g, and 18b, which exhibited potency comparable to celecoxib. The most promising candidates underwent further in vivo evaluation utilizing the carrageenan-induced paw edema model, exhibiting significant anti-edematous activity. Compound 8g demonstrated the most significant and enduring reduction in paw swelling and tissue weight, surpassing the efficacy of reference drugs. Mechanistic investigations demonstrated significant downregulation of NF-κB and its downstream inflammatory mediators, such as COX-2, iNOS, TNF-α, and IL-1β. The lead compounds demonstrated notable analgesic activity in the hot plate test, with no observable hepatic, renal, or cardiac toxicity. Molecular docking and molecular dynamics simulations demonstrated stable binding in the COX-2 active site, and in silico ADME analysis suggested favorable drug-likeness. These findings collectively identify compound 8g as a promising multi-target anti-inflammatory candidate for further development.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"8225-8251"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computational screening of Alternaria metabolites as potential DPP-4 inhibitors: ADMET, molecular docking, molecular dynamics, and network pharmacology analysis. 交替孢代谢物作为潜在DPP-4抑制剂的计算筛选：ADMET、分子对接、分子动力学和网络药理学分析。

IF 4.3 2区化学

Molecular Diversity Pub Date : 2026-10-01 Epub Date: 2026-06-05 DOI: 10.1007/s11030-026-11605-3

Piyush Kumar, Sai Anand Kannakazhi Kantari, Malleswara Dharanikota

{"title":"Computational screening of Alternaria metabolites as potential DPP-4 inhibitors: ADMET, molecular docking, molecular dynamics, and network pharmacology analysis.","authors":"Piyush Kumar, Sai Anand Kannakazhi Kantari, Malleswara Dharanikota","doi":"10.1007/s11030-026-11605-3","DOIUrl":"10.1007/s11030-026-11605-3","url":null,"abstract":"Type 2 diabetes (T2D) remains a major global health challenge, underscoring the need for safer and more effective therapeutic agents. Although fungi are rich sources of structurally diverse bioactive metabolites, the antidiabetic potential of the genus Alternaria remains poorly explored. Here, we investigated 278 Alternaria-derived metabolites as potential inhibitors of dipeptidyl peptidase-4 (DPP-4), a clinically validated target involved in glucose homeostasis through incretin regulation. An integrated computational pipeline combining ADMET profiling, molecular docking, 300 ns molecular dynamics simulations, MM-PBSA binding free-energy calculations, principal component analysis (PCA) and free energy landscape (FEL) mapping, clustering, and network pharmacology was employed to identify and characterize lead compounds. Among the screened metabolites, Anthrininone B (AntB) emerged as the most promising candidate, showing binding behaviour comparable to, and slightly more favourable than, the reference inhibitor Linagliptin (Lin). AntB exhibited the most favourable mean MM-PBSA binding free energy (- 26.77 ± 8.20 kcal/mol), stable conformational convergence, a compact free-energy landscape, and representative clustered conformations consistent with persistent binding. Mechanistically, AntB transitioned from the S2 extensive tunnel into a deeply seated catalytic pose, forming stable interactions with Glu206, Tyr662/Tyr666, and Ser630, while maintaining overall protein stability. Network pharmacology further suggested that AntB may modulate multiple T2D-relevant pathways, including insulin resistance, inflammation, oxidative stress, and β-cell preservation. Collectively, these findings identify Alternaria metabolites, particularly AntB, as promising scaffolds for antidiabetic drug discovery and warrant further experimental validation.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"8515-8535"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design, synthesis, antibacterial activity evaluation, and mechanism of action study of novel pyrrolidine derivatives containing sulfonamide structures. 新型磺胺类吡咯烷衍生物的设计、合成、抗菌活性评价及作用机理研究。

IF 4.3 2区化学

Molecular Diversity Pub Date : 2026-10-01 Epub Date: 2026-06-15 DOI: 10.1007/s11030-026-11609-z

Tonghong Xia, Laiqi Li, Xinyu Wang, Jianhong Li, Yazhen Chen, Lei Yu, Xiaokang Lv, Song Bai

{"title":"Design, synthesis, antibacterial activity evaluation, and mechanism of action study of novel pyrrolidine derivatives containing sulfonamide structures.","authors":"Tonghong Xia, Laiqi Li, Xinyu Wang, Jianhong Li, Yazhen Chen, Lei Yu, Xiaokang Lv, Song Bai","doi":"10.1007/s11030-026-11609-z","DOIUrl":"10.1007/s11030-026-11609-z","url":null,"abstract":"Bacterial biofilms serve as innate protective frameworks, sheltering embedded microbes to sustain their survival while potentially enhancing antimicrobial resistance by blocking bactericide penetration. While extensive research has focused on planktonic bacteria, biofilm recalcitrance remains understudied, leaving conventional antimicrobials often ineffective against these sessile communities. This underscores an urgent need for next-generation agents with specialized biofilm-inhibiting properties to enabling effective antibacterial therapy; in this study, we used pyrrolidine-3-carboxylic acid as a starting material to synthesize a series of sulfonamide-containing pyrrolidine derivatives via an active coupling reaction. Compound A14 exhibited the strongest activity, with an EC₅₀ value of 38.33 μg/mL against Xanthomonas oryzae pv. oryzae (Xoo). Mechanistic investigations revealed that A14 suppresses extracellular polymeric substance (EPS) biosynthesis and bacterial motility-key drivers of pathogenicity, biofilm development, and plant cell wall degradation. Conductivity measurements and protein leakage assays confirmed that A14 disrupts multiple Xoo physiological functions, positioning it as a promising antimicrobial candidate targeting core mechanisms of bacterial plant diseases.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"7475-7496"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis and molecular characterization of a novel FA-ADH-GMS conjugated pH-responsive lipid for targeted drug delivery. 一种新型FA-ADH-GMS偶联ph响应脂质的合成和分子表征。

IF 4.3 2区化学

Molecular Diversity Pub Date : 2026-10-01 Epub Date: 2026-04-26 DOI: 10.1007/s11030-026-11562-x

Sai Ramya Bodagala, Prasanthi Samathoti

引用次数: 0

An integrated machine learning and chemical space network approach for the design of potent epigenetic HDAC6 inhibitors for targeting neurological disorders. 一种集成的机器学习和化学空间网络方法，用于设计针对神经系统疾病的有效表观遗传HDAC6抑制剂。

IF 4.3 2区化学

Molecular Diversity Pub Date : 2026-10-01 Epub Date: 2026-05-23 DOI: 10.1007/s11030-026-11591-6

Indrasis Dasgupta, Rupchand Pandit, Vijeta Jha, Rahul Verma, Insaf Ahmed Qureshi, Sk Abdul Amin, Shovanlal Gayen

{"title":"An integrated machine learning and chemical space network approach for the design of potent epigenetic HDAC6 inhibitors for targeting neurological disorders.","authors":"Indrasis Dasgupta, Rupchand Pandit, Vijeta Jha, Rahul Verma, Insaf Ahmed Qureshi, Sk Abdul Amin, Shovanlal Gayen","doi":"10.1007/s11030-026-11591-6","DOIUrl":"10.1007/s11030-026-11591-6","url":null,"abstract":"Histone deacetylase 6 (HDAC6) is increasingly recognized as a key regulator of cytoskeletal dynamics and intracellular transport in both neurodevelopmental and neurodegenerative disorders. Despite the large number of HDAC6 inhibitors reported, only a few have shown effective in vivo activity in neurological disease models. In this context, machine-learning (ML) approaches offer a powerful strategy for extracting chemical, physical, and biological features from a large and complex dataset of 4307 HDAC6 inhibitors. The current research aimed to develop high-quality ML-based classification frameworks to identify pivotal structural fingerprints of HDAC6 inhibitors. Additionally, chemical space network (CSN) construction, scaffold diversity exploration, and matched molecular series analysis were performed to provide an extensive computational investigation of HDAC6 inhibitors. The research highlighted the significance of various scaffolds, which may play a promising role in HDAC6 inhibition. This integrated computational strategy offers a potent platform for interpreting and predicting HDAC6 inhibitory activity, thereby facilitating lead optimization and the rational design of novel therapeutics.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"8377-8394"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148003935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the renoprotective potential of Beta vulgaris in diabetic nephropathy: an integrated network pharmacology, molecular docking and dynamics simulation study. 探索寻常β在糖尿病肾病中的肾保护潜能：综合网络药理学、分子对接和动力学模拟研究。

IF 4.3 2区化学

Molecular Diversity Pub Date : 2026-10-01 Epub Date: 2026-05-23 DOI: 10.1007/s11030-026-11585-4

Abhishek Sehrawat, Yogesh Singh, Khushi Gupta, Suresh Thareja, Jasvinder Singh Bhatti

{"title":"Exploring the renoprotective potential of Beta vulgaris in diabetic nephropathy: an integrated network pharmacology, molecular docking and dynamics simulation study.","authors":"Abhishek Sehrawat, Yogesh Singh, Khushi Gupta, Suresh Thareja, Jasvinder Singh Bhatti","doi":"10.1007/s11030-026-11585-4","DOIUrl":"10.1007/s11030-026-11585-4","url":null,"abstract":"Diabetic Nephropathy (DN) is a leading cause of end-stage renal failure globally. Beta vulgaris (BV), also known as beetroot, is a functional food that has shown promise in managing various metabolic disorders, including cancer, diabetes, cardiovascular disease, and liver disease, due to its anti-hypertensive, antioxidant, and anti-inflammatory properties. However, its role in DN and the underlying molecular mechanisms are not yet fully elucidated. Our study aimed to investigate the therapeutic potential of BV in DN through an integrated approach involving network pharmacology, molecular docking, and molecular dynamics simulation. The study identified 11 bioactive compounds from BV and 329 intersecting DN-related gene targets using databases such as IMPPAT, SwissTargetPrediction, DisGeNET, CTD, and GeneCards, all of which are related to DN. The protein-protein interaction networks constructed and visualized using STRING and Cytoscape v3.9.1, revealed key gene targets, including MAPK3, MAPK1, AKT1, IL1B, and MAPK14. Furthermore, GO and KEGG enrichment analysis highlighted their involvement in pathways such as the AGE-RAGE, PI3K-AKT, and cAMP signaling pathways. In addition, the molecular docking demonstrated significant binding energies (≤ - 5 kcal/mol) for bioactives such as Caffeic acid and Ferulic acid with MAPK1, MAPK3, and AKT1. Further, the MD simulation confirmed stable interactions for all proteins, emphasizing the BV's multi-pathway therapeutic mechanisms in the management of DN. Altogether, this computational study highlighted BV as a candidate nephroprotective agent, providing a comprehensive insight into its molecular mechanisms in treating DN. The integrated molecular mechanistic study highlighted the ameliorative role of BV against DN, which further paves the way for future research in DN therapeutics.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"8355-8376"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148003961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Improving aptamer binding affinity for HN protein of newcastle disease virus: molecular dynamics simulations and MM/GBSA calculations studies. 提高新城疫病毒HN蛋白的适体结合亲和力：分子动力学模拟和MM/GBSA计算研究

IF 4.3 2区化学

Molecular Diversity Pub Date : 2026-10-01 Epub Date: 2026-05-03 DOI: 10.1007/s11030-026-11573-8

Shuang Jiang, Xu Wen, Xiaoling Zheng, Xue Wang, Xianlu Lei, Yong Xie, Tao Le

{"title":"Improving aptamer binding affinity for HN protein of newcastle disease virus: molecular dynamics simulations and MM/GBSA calculations studies.","authors":"Shuang Jiang, Xu Wen, Xiaoling Zheng, Xue Wang, Xianlu Lei, Yong Xie, Tao Le","doi":"10.1007/s11030-026-11573-8","DOIUrl":"10.1007/s11030-026-11573-8","url":null,"abstract":"Aptamers, as single-stranded DNA (ssDNA) or RNA oligonucleotides, are pivotal in biosensing due to their high affinity. However, excessive lengths of these nucleic acid probes can impair their binding affinity and target recognition efficiency. Traditional optimization methods, such as static structural modeling, fail to capture the dynamic interactions between aptamers and biological macromolecules. Therefore, optimizing aptamer length to enhance affinity while maintaining effective target recognition is crucial. Here, we employed 600ns molecular dynamics (MD) simulations using the amberff14sb and parmbsc1 force fields, alongside molecular mechanics/generalized Born surface area (MM/GBSA) free energy calculations to optimize the binding affinity of a ssDNA aptamer targeting the hemagglutinin-neuraminidase (HN) protein-a critical surface receptor of Newcastle disease virus (NDV) responsible for viral attachment and entry. By systematically truncating the aptamer sequence guided by normalized criteria to eliminate length bias, we identified a 10-nucleotide variant (fqh-2) that exhibited a hydrogen bond efficiency ratio (HBER) of 1.055 and a binding free energy efficiency ratio (BFEER) of -5.124 kcal/mol, reflecting enhanced interactions with the HN protein. Furthermore, a graphene oxide (GO)-based fluorescence quenching assay confirmed a threefold increase in binding affinity for the optimized aptamer, aligning with computational predictions. This study not only provides a dynamic structure-guided framework for aptamer optimization but also lays a theoretical foundation for further advancements in optimizing and tailoring aptamers for specific applications.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"8161-8175"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Imidazole Scaffolds against Staphylococcus aureus and MRSA: a medicinal chemistry review. 咪唑支架抗金黄色葡萄球菌和MRSA：药物化学综述。

IF 4.3 2区化学

Molecular Diversity Pub Date : 2026-10-01 Epub Date: 2026-05-11 DOI: 10.1007/s11030-026-11580-9

Supriyo Saha, Muskan Singh, Nikita Thapliyal, Shakir Ahamad, Shahnawaz Ali Bhat, Vikash Jakhmola

{"title":"Imidazole Scaffolds against Staphylococcus aureus and MRSA: a medicinal chemistry review.","authors":"Supriyo Saha, Muskan Singh, Nikita Thapliyal, Shakir Ahamad, Shahnawaz Ali Bhat, Vikash Jakhmola","doi":"10.1007/s11030-026-11580-9","DOIUrl":"10.1007/s11030-026-11580-9","url":null,"abstract":"Staphylococcus aureus infections remain a major clinical challenge due to rapid acquisition of antimicrobial resistance, exemplified by Methicillin-Resistant Staphylococcus aureus. The imidazole scaffold has attracted sustained interest owing to its chemical versatility and broad pharmacological relevance. This review provides the first comprehensive and critical summary of recent advances in the synthesis and anti-staphylococcal activity of structurally diverse imidazole derivatives, including benzimidazoles, metal complexes, mercapto- and polycyclic analogues, and hybrid conjugates with bioactive motifs such as indole, berberine, and rifamycin. Both conventional and enabling methodologies (microwave- and ultrasound-assisted synthesis) are evaluated, with key transformations encompassing condensations, transition-metal-catalyzed couplings, complexation, El-Saghier, and Groebke-Blackburn-Bienaymé reactions. Structure-activity relationship analyses reveal that indole-, rifamycin-, berberine-, and N-aryl-substituted imidazoles exhibit superior potency against resistant strains, whereas hydroxynaphthalene, 2-phenyl-benzimidazole, imidazothiadiazole, and isatin analogues often show diminished activity. Collectively, these insights provide a rational framework for designing next-generation imidazole-based anti-staphylococcal agents, while underscoring the need for comprehensive profiling of stability, toxicity, and PK/PD properties to enable clinical translation.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"7645-7713"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of potent biphenyl-macolacin derivatives through a lysine-T/CDHA iterative scanning (LTIS) strategy followed by chemical ligation-based modifications. 通过赖氨酸- t /CDHA迭代扫描（LTIS）策略，以及基于化学连接的修饰，发现有效的联苯-麦可拉星衍生物。

IF 4.3 2区化学

Molecular Diversity Pub Date : 2026-10-01 Epub Date: 2026-07-11 DOI: 10.1007/s11030-026-11663-7

Xiaoshu Jing, Kaixuan Song, Biyao Liu, Kang Jin

{"title":"Discovery of potent biphenyl-macolacin derivatives through a lysine-T/CDHA iterative scanning (LTIS) strategy followed by chemical ligation-based modifications.","authors":"Xiaoshu Jing, Kaixuan Song, Biyao Liu, Kang Jin","doi":"10.1007/s11030-026-11663-7","DOIUrl":"10.1007/s11030-026-11663-7","url":null,"abstract":"The antibiotic biphenyl-macolacin (Bip-macolacin) is a promising drug candidate with good activity against Gram-negative bacteria including several colistin-resistant pathogens, providing a potential structural motif for developing novel antibiotics. Considering the importance of efficient and effective structural optimization in medicinal chemistry studies, we herein report a lysine-T/CDHA iterative scanning (LTIS) strategy to produce Bip-macolacin analogues and identify the modifiable sites, followed by structural derivatization through chemical ligation chemistry. Using this approach, four classes of Bip-macolacin derivatives were prepared conveniently, several of which exhibited antibacterial activities comparable or better than those of Bip-macolacin. The efficacy of representative analogues 5, 18, and 46 was also demonstrated by the resistance development evaluation and hemolysis assay. From this study, a systematic structure-activity relationship of Bip-macolacin was established as a reference for further development of Bip-macolacin-based antibiotics. This novel and powerful strategy also provides more opportunities and valuable options for the structural optimization in future research on peptide therapeutics.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"7513-7529"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0