Saragatsis Michail A, Kinsella Gemma K, Curtin James F, Zhang Tao
School of Food Science and Environmental Health, Technological University of Dublin, Grangegorman Lower, Dublin 7, D07 ADY7, Dublin, Ireland.
Food Innovation and Health Research Centre, Technological University of Dublin, Grangegorman Lower, Dublin 7, D07 ADY7, Dublin, Ireland.
ChemMedChem. 2025 Nov 6;20(21):e202500365. doi: 10.1002/cmdc.202500365. Epub 2025 Sep 3.
Cancer, a leading cause of global mortality, is characterized by uncontrolled cell proliferation and remains a significant therapeutic challenge due to drug resistance and treatment failures. Despite advancements in targeted therapies, novel agents are still in strong demand. Benzosuberane, a bicyclic scaffold present in natural products such as colchicine and theaflavin, has emerged as a promising structural core in cancer therapeutics due to its structural flexibility and diverse biological activities, including antitumor, anti-inflammatory, and antimicrobial effects. This review consolidates the computational insights driving the design of benzosuberane-based compounds as effective antitumor agents. Focusing on molecular docking studies, it highlights the interaction profiles with various target classes, including antivascular agents, kinase inhibitors, receptor modulators, and DNA-intercalators. These interactions regulate critical oncogenic pathways, offering mechanistic details that highlight the compounds' potential for enhanced specificity and therapeutic efficacy. Among the cancer targets, benzosuberane-based compounds acting as antivascular agents and DNA-targeting agents emerged as the most promising, based on consistent binding affinities, cytotoxicity, and binding interaction profiles across breast, lung, and colon cancer cell lines. By summarizing the structural and molecular requirements for benzosuberane-mediated modulation of cancer pathway and identifying promising compounds, this work aims to guide future research and advance drug discovery pipelines.
癌症是全球主要死因之一，其特征是细胞不受控制地增殖，并且由于耐药性和治疗失败，仍然是一个重大的治疗挑战。尽管靶向治疗取得了进展，但新型药物仍有很大需求。苯并降冰片烷是秋水仙碱和茶黄素等天然产物中存在的一种双环骨架，由于其结构灵活性和多种生物活性，包括抗肿瘤、抗炎和抗菌作用，已成为癌症治疗中一个有前景的结构核心。本综述整合了推动设计基于苯并降冰片烷的化合物作为有效抗肿瘤药物的计算见解。重点关注分子对接研究，突出了与各种靶标类别的相互作用概况，包括抗血管生成剂、激酶抑制剂、受体调节剂和DNA嵌入剂。这些相互作用调节关键的致癌途径，提供了机制细节，突出了这些化合物在提高特异性和治疗效果方面的潜力。在癌症靶标中，基于苯并降冰片烷的化合物作为抗血管生成剂和DNA靶向剂，基于在乳腺癌、肺癌和结肠癌细胞系中一致的结合亲和力、细胞毒性和结合相互作用概况，成为最有前景的药物。通过总结苯并降冰片烷介导的癌症途径调节的结构和分子要求，并识别有前景的化合物，这项工作旨在指导未来的研究并推进药物发现流程。
