{"title":"Ring opening of epoxides: a facile approach towards the synthesis of polyketides and related stereoenriched natural products: a review.","authors":"Madiha Hanif, Asim Mansha, Kulsoom Ghulam Ali, Muhammad Athar Saeed, Shahid Mahmood, Aijaz Rasool Chaudhry, Ahmad Irfan, Aqsa Mushtaq, Ameer Fawad Zahoor","doi":"10.1007/s11030-024-11057-7","DOIUrl":"10.1007/s11030-024-11057-7","url":null,"abstract":"<p><p>Epoxides are significant heterocycles in the structural makeup of a variety of natural products. Their ring-opening reactions have emerged as a versatile and efficient strategies for synthesizing a variety of functionalized molecules. Such reactions have been extensively applied towards the preparation of complex naturally occurring products. The focus on epoxide ring-opening reactions within the scientific community has been increased, influenced by the goal to understand the synthesis of compounds that are important for their biological and structural significance. In this article, we have provided a concise account on the applications of epoxide's ring cleavage towards the syntheses of polyketides and related naturally occurring compounds, documented since last decade (2014-2023).</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"4919-4952"},"PeriodicalIF":3.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799091","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}
{"title":"Research progress of SHP-1 agonists as a strategy for tumor therapy.","authors":"Xiaoyue Liu, Qindi He, Shuding Sun, Xun Lu, Yadong Chen, Shuai Lu, Zhijie Wang","doi":"10.1007/s11030-024-11059-5","DOIUrl":"10.1007/s11030-024-11059-5","url":null,"abstract":"<p><p>Src homology-2 domain-containing protein tyrosine phosphatase 1 (SHP-1) is a member of protein tyrosine phosphatase (PTP) family, and serves as a crucial negative regulator of various oncogenic signaling pathways. The development of SHP-1 agonists has garnered extensive research attention and is considered as a promising strategy for treating tumors. In this review, we comprehensively analyze the advancements of SHP-1 agonists, focusing on their structures and biological activities. Based on the structure skeletons, we classify these SHP-1 agonists as kinase inhibitors, sorafenib derivatives, obatoclax derivatives, lithocholic acid derivatives and thieno[2,3-b]quinoline derivatives. Additionally, we discuss the potential opportunities and challenges for developing SHP-1 agonists. It is hoped that this review will provide inspiring insights into the discovery of drugs targeting SHP-1.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"4953-4961"},"PeriodicalIF":3.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909084","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}
Molecular DiversityPub Date : 2025-10-01Epub Date: 2025-01-11DOI: 10.1007/s11030-024-11045-x
Jinglei Xu, Jiahao Yuan, Wenxin Wang, Xiaoning Zhu, Jialong Li, Yule Ma, Shaojie Liu, Jie Feng, Yadong Chen, Tao Lu, Hongmei Li
{"title":"Small molecules that targeting p53 Y220C protein: mechanisms, structures, and clinical advances in anti-tumor therapy.","authors":"Jinglei Xu, Jiahao Yuan, Wenxin Wang, Xiaoning Zhu, Jialong Li, Yule Ma, Shaojie Liu, Jie Feng, Yadong Chen, Tao Lu, Hongmei Li","doi":"10.1007/s11030-024-11045-x","DOIUrl":"10.1007/s11030-024-11045-x","url":null,"abstract":"<p><p>The p53 protein is regarded as the \"Guardian of the Genome,\" but its mutation is tumor progression and present in more than half of malignant tumors. The pro-metastatic property of mutant p53 makes a strong argument for targeting mutant p53 with new therapeutic strategies. However, mutant p53 was considered as a challenging target for drug discovery due to the lack of small molecular binding pockets. Among them, mutant p53 Y220C creates a narrow crevice since the side chains dynamics on protein surface, which is suitable for designing small molecules to occupy the cavity and recovery the tumor suppressing function. Here, we describe the mechanism of p53 related signal pathway and how p53 Y220C regulate the tumorigenesis. We review the two types of p53 Y220C modulators including restoring the conformation of mutant p53 Y220C protein to wild-type p53 protein and recruiting histone acetyltransferase p300/CBP to acetylate p53 Y220C thus enables p53 Y220C dependent upregulation of apoptotic genes and downregulation of DNA damage response pathways. We also report clinical advances and challenges of these molecules in p53 Y220C medicated tumor therapy.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"4861-4873"},"PeriodicalIF":3.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969217","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}
{"title":"Late-stage-functionalization of anti-depressant molecule buspirone.","authors":"Yalin Guo, Debin Yang, Bo Hu, Yongtao Duan, Yibing Cheng, Yu Tang, Caili Guo, Yuanzhe Li, Bing Yu","doi":"10.1007/s11030-024-11029-x","DOIUrl":"10.1007/s11030-024-11029-x","url":null,"abstract":"<p><p>Buspirone, a well-established anxiolytic agent, has gained attention for its potential role as an antidepressant, primarily due to its unique pharmacological profile and the ability to modulate serotonin receptors effectively. Late-stage functionalization is considered as a pivotal strategy in drug synthesis that enhances the therapeutic efficacy of existing molecules. This review summarizes various late-stage functionalization techniques applicable to Buspirone, including photocatalyzed, metal-catalyzed, and enzyme-catalyzed reactions.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"5033-5043"},"PeriodicalIF":3.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692520","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}
{"title":"Recent advances in microbially derived chlorinated antiparasitic compounds.","authors":"Samriti Saklani, Shruti Chaudhari, Gayatri Shukla, Harishankar Gound, Dewashish Awasarmol, Ravindra Taware","doi":"10.1007/s11030-024-11018-0","DOIUrl":"10.1007/s11030-024-11018-0","url":null,"abstract":"<p><p>Parasitic diseases remain a significant global health challenge, especially in developing countries, contributing to approximately one million deaths annually. Notably, among the 143 FDA-approved antiparasitic drugs, thirty-four possess chlorine in their chemical structure, highlighting the importance of chlorine substitution. This underscores the significance of chlorine atoms in elucidating structure-activity relationships crucial for drug discovery, aiming to develop safer, more selective, and environmentally friendly molecules with enhanced efficacy. Of particular interest some are naturally occurring chlorinated metabolites derived from PKS, NRPS, and PKS-NRPS biosynthetic pathways, which offer the potential for further manipulation. However, there is limited literature on antiparasitic chlorinated compounds from microbial sources. To address this, we conducted a comprehensive literature survey from 1963 to the present, identifying 28 chlorinated compounds with confirmed antiparasitic properties. This review underscores the potential of enzymatic machinery for selective chlorine substitution, offering insights for biochemists and synthetic chemists to develop versatile chlorinated compounds through synthetic biology, combinatorial chemistry, and organic synthesis.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"4837-4860"},"PeriodicalIF":3.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542813","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}
{"title":"Structural aspects of HIV-1 integrase inhibitors: SAR studies and synthetic strategies.","authors":"Pallavi Barik, Shankar Gupta, Gurpreet Singh, Sanjay Kumar Bharti, Vivek Asati","doi":"10.1007/s11030-024-11068-4","DOIUrl":"10.1007/s11030-024-11068-4","url":null,"abstract":"<p><p>Acquired immunodeficiency syndrome (AIDS) poses a significant threat to life. Antiretroviral therapy is employed to diminish the replication of the human immunodeficiency virus (HIV), extending life expectancy and improving the quality of patients' lives. These HIV-1 integrase inhibitors form robust covalent interactions with Mg<sup>2+</sup> ions, contributing to their tight binding, thereby inhibiting the integration of viral DNA into the CD4 cell DNA. The second-generation INSTIs, the most recently approved, exhibit a higher genetic barrier compared to first-generation drugs. Hence, there is a need to develop novel and safe compounds as inhibitors of HIV-1 integrase. This article presents an overview of the current landscape of anti-HIV-1 integrase inhibitors, emphasizing the structure-activity relationship (SAR) of small molecules. The molecules discussed include monocyclic rings consisting of triazoles moiety, and pyrimidine analog along with bicyclic rings with nitrogen-containing moieties. Researchers are exploring anti-HIV-1 integrase inhibitors from natural sources like marine environments, plant extracts, and microbial products, emphasizing the importance of diverse bioactive compounds in combating the virus, which have also been included in the manuscript. The current manuscript will be helpful to the scientific community engaged in the manipulation of small molecules as anti-HIV integrase inhibitors for designing newer leads.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"4963-4997"},"PeriodicalIF":3.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845484","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}
Molecular DiversityPub Date : 2025-10-01Epub Date: 2024-07-10DOI: 10.1007/s11030-024-10917-6
Juan Fu, Lin Mao, Yu Jiao, Desheng Mei, Yadong Chen
{"title":"Elucidating CTLA-4's role in tumor immunity: a comprehensive overview of targeted antibody therapies and clinical developments.","authors":"Juan Fu, Lin Mao, Yu Jiao, Desheng Mei, Yadong Chen","doi":"10.1007/s11030-024-10917-6","DOIUrl":"10.1007/s11030-024-10917-6","url":null,"abstract":"<p><p>Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) emerges as a key single-chain transmembrane glycoprotein predominantly expressed in effector T cells and regulatory T cells. It plays a crucial role in tumor immunity by modulating T cell responses. Specifically, CTLA-4 dampens T cell activation and proliferation while bolstering the survival of regulatory T cell through its competitive interaction with B7 family molecules, thereby aiding tumor cells in eluding immune detection. Given CTLA-4's significant influence on tumor immune dynamics, an array of anti-CTLA-4 antibody therapeutics have been clinically developed to combat various malignancies, including melanoma, renal cell carcinoma, colorectal carcinoma, hepatocellular carcinoma, non-small cell lung carcinoma, and pleural mesothelioma, demonstrating notable clinical therapeutic effects. This paper aims to delve into CTLA-4's integral role in tumor immunity and to encapsulate the latest advancements in the clinical research of anti-CTLA-4 antibody.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"5075-5084"},"PeriodicalIF":3.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562344","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}
Molecular DiversityPub Date : 2025-10-01Epub Date: 2024-11-04DOI: 10.1007/s11030-024-11030-4
Chuang Song, Mosstafa Kazemi
{"title":"Based on magnetically recoverable catalysts: a green strategy to sulfonamides.","authors":"Chuang Song, Mosstafa Kazemi","doi":"10.1007/s11030-024-11030-4","DOIUrl":"10.1007/s11030-024-11030-4","url":null,"abstract":"<p><p>The synthesis of sulfonamides, a class of compounds with significant pharmaceutical and medicinal applications, has seen remarkable advancements with the advent of magnetic nanocatalysts. Magnetic nanocomposites are one of the most efficient and widely used catalysts, and they are in complete harmony with the principles of modern green chemistry from the point of view of catalysis. These catalysts, typically composed of metal complexes supported on magnetic nanoparticles, offer unique advantages such as ease of recovery and reusability, which are crucial for sustainable and eco-friendly chemical processes. This review comprehensively examines recent developments in applying magnetic nanocatalysts to prepare sulfonamides. Key focus areas include the design and synthesis of various magnetic nanocatalysts (MNC), their catalytic performance in different reaction conditions, and mechanistic insights into their catalytic activity. By summarizing the latest research and technological advancements, this article aims to provide a valuable resource for researchers and practitioners in catalysis and pharmaceutical chemistry.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"5045-5074"},"PeriodicalIF":3.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567168","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}
Molecular DiversityPub Date : 2025-10-01Epub Date: 2024-12-01DOI: 10.1007/s11030-024-11053-x
Hiren R Chaudhary, Divyang M Patel
{"title":"New frontiers in multicomponent mechanosynthesis for organic molecules: modern marvels.","authors":"Hiren R Chaudhary, Divyang M Patel","doi":"10.1007/s11030-024-11053-x","DOIUrl":"10.1007/s11030-024-11053-x","url":null,"abstract":"<p><p>In the past, mechanochemical approaches in organic synthesis were largely overlooked, but their perception within the synthetic community has shifted in recent years, marking a trend toward becoming mainstream. Mechanochemical multicomponent organic synthesis has garnered significant interest from both the academic and industrial chemical sectors. The efficiency and environmental friendliness of procedures conducted through mechanical activation have established mechanical procedures as prominent green techniques. Notably, utilizing solid starting materials under mechanochemical conditions empowers the development of novel multicomponent reactions that are often unfeasible in traditional solution-based processes. This capability not only enhances the diversity of accessible organic compounds but also sparks new avenues for innovative synthetic strategies. This approach facilitates the effective fulfillment of sustainable chemistry goals. In this context, we emphasize the major progress and advancements in mechanochemical multicomponent reactions from 2017 to 2024. This article covers the foremost multicomponent mechanosynthesis for developing organic molecules through carbon-carbon and carbon-heteroatom coupling reactions and multicomponent mechanosynthesis for monocyclic and fused heterocycles.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"4875-4918"},"PeriodicalIF":3.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765297","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}
{"title":"MMADPE: drug repositioning based on multi-hop graph Mamba aggregation with dual-modality graph positional encoding.","authors":"Pengli Lu, Mingxu Li, Fentang Gao","doi":"10.1007/s11030-025-11349-6","DOIUrl":"https://doi.org/10.1007/s11030-025-11349-6","url":null,"abstract":"<p><p>Drug repositioning (DR) has emerged as a critical research strategy for uncovering novel therapeutic applications of existing drugs, demonstrating considerable clinical significance. Despite promising advancements in computational methods for predicting drug-disease associations, most algorithms exhibit three major limitations. First, they inadequately capture high-order relationships within drug-disease networks. Second, they fail to concurrently model both local interaction strengths and global network topologies. Most importantly, current models lack biological interpretability and are incapable of extracting meaningful biological patterns from numerical data. To address these challenges, we propose a novel drug repositioning framework, MMADPE. This framework constructs a similarity network supporting multi-hop aggregation and leverages the linear complexity of Graph Mamba to efficiently integrate multi-order neighborhood information, thereby significantly enhancing the modeling of long-range drug-disease interactions. Subsequently, a dual-modal graph positional encoding is employed, capturing global network topology via Laplacian eigenvectors and characterizing local node association strengths through random walk statistics. Finally, the framework incorporates a GraphGPS hybrid architecture that fuses gated graph convolution with Transformer attention mechanisms to extract molecular biochemical features and their semantic relationships, achieving a deep integration of topological structures and biological semantics. Extensive experiments on three benchmark datasets demonstrate that MMADPE consistently outperforms state-of-the-art methods in drug repositioning tasks. Notably, case studies on two common diseases combined with molecular docking experiments not only validate the effectiveness of our approach but also provide novel mechanistic insights into MMADPE's ability to identify previously unrecognized drug-disease associations.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197852","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}