Molecular Docking and Target‐Specific Binding Profiles of Benzosuberane‐Based Compounds

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.

• Publication year

  2025

• Venue

  ChemMedChem

• Publication date

  2025-09-03

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1002/cmdc.202500365PMID 40902196PMCID 12597223
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Molecular Docking and Target‐Specific Binding Profiles of Benzosuberane‐Based Compounds

  2025cited by this paper
• Insights into artificial intelligence utilisation in drug discovery

  2024cited by this paper
• Structural insights into the DNA topoisomerase II of the African swine fever virus

  2024cited by this paper
• An allosteric inhibitor of RhoGAP class-IX myosins suppresses the metastatic features of cancer cells

  2024cited by this paper
• A Mini Review of Novel Topoisomerase II Inhibitors as Future Anticancer Agents

  2023cited by this paper
• Novel pyrrolone-fused benzosuberene MK2 inhibitors: synthesis, pharmacophore modelling, molecular docking, and anti-cancer efficacy evaluation in HNSCC cells

  2023cited by this paper
• In-silico guided chemical exploration of KDM4A fragments hits

  2023cited by this paper
• The History and Development of HER2 Inhibitors

  2023cited by this paper
• Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management

  2023cited by this paper
• Advancements of ALK inhibition of non-small cell lung cancer: a literature review

  2023cited by this paper
• Synthesis of tricyclic and tetracyclic benzo[6,7]cycloheptane derivatives linked morpholine moiety as CDK2 inhibitors

  2023cited by this paper
• Design Synthesis, Molecular Docking, and in vitro Anticancer and Antibacterial Evaluation of Novel 2-(9- chloro-2,3-dimethyl-6,7-dihydro-5H-benzo [7] annulen-8-yl)-3-thiazolidin-4one

  2023cited by this paper
• The emerging roles of lysine-specific demethylase 4A in cancer: Implications in tumorigenesis and therapeutic opportunities

  2023cited by this paper
• A comprehensive analysis of the role of molecular docking in the development of anticancer agents against the cell cycle CDK enzyme

  2023cited by this paper
• A Computational QSAR, Molecular Docking and In Vitro Cytotoxicity Study of Novel Thiouracil-Based Drugs with Anticancer Activity against Human-DNA Topoisomerase II

  2022cited by this paper
• Recent Advances with KDM4 Inhibitors and Potential Applications.

  2022cited by this paper
• Inhibition of the CDK2 and Cyclin A complex leads to autophagic degradation of CDK2 in cancer cells

  2022cited by this paper
• Review: Aminopeptidases in Cancer, Biology and Prospects for Pharmacological Intervention.

  2022cited by this paper
• Synthesis, Structure–Activity Relationships, and Parasitological Profiling of Brussonol Derivatives as New Plasmodium falciparum Inhibitors

  2022cited by this paper
• Synthetic Approaches and Pharmacological Attributes of Benzosuberone Skeleton.

  2022cited by this paper
• Molecular Docking as a Therapeutic Approach for Targeting Cancer Stem Cell Metabolic Processes

  2022cited by this paper
• DNA intercalators as anticancer agents

  2022cited by this paper
• Novel 6,7,8-trihydrobenzo[6',7']cyclohepta[2',1'-e]pyrazolo[2,3-a]pyrimidine derivatives as Topo IIα inhibitors with potential cytotoxic activity.

  2022cited by this paper
• A comprehensive review of SHP2 and its role in cancer

  2022cited by this paper
• Efficient Exploration of Chemical Space with Docking and Deep Learning.

  2021cited by this paper
• Exploring Artificial Intelligence in Drug Discovery: A Comprehensive Review

  2021cited by this paper
• Role of Small Molecule Targeted Compounds in Cancer: Progress, Opportunities, and Challenges

  2021cited by this paper
• New approaches and procedures for cancer treatment: Current perspectives

  2021cited by this paper
• AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings

  2021cited by this paper
• Small molecules in targeted cancer therapy: advances, challenges, and future perspectives

  2021cited by this paper
• Recent advances in total syntheses of natural products containing the benzocycloheptane motif.

  2021cited by this paper
• Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

  2020cited by this paper
• The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer

  2020cited by this paper
• SHP2 is a multifunctional therapeutic target in drug resistant metastatic breast cancer

  2020cited by this paper
• Dual inhibitors of human DNA topoisomerase II and other cancer-related targets.

  2020cited by this paper
• Invited submission by the editor marek los vascular disrupting agents in cancer therapy.

  2020cited by this paper
• Recent Advances of SHP2 Inhibitors in Cancer Therapy: Current Development and Clinical Application.

  2020cited by this paper
• A New Family of Jumonji C Domain-Containing KDM Inhibitors Inspired by Natural Product Purpurogallin

  2020cited by this paper
• The Expressions and Mechanisms of Sarcomeric Proteins in Cancers

  2020cited by this paper
• MAPKAPK2 (MK2) inhibition mediates radiation-induced inflammatory cytokine production and tumor growth in head and neck squamous cell carcinoma

  2019cited by this paper
• Colchicine: Isolation, LC–MS QTof Screening, and Anticancer Activity Study of Gloriosa superba Seeds

  2019cited by this paper
• Molecules

  2019cited by this paper
• Development and structure-activity relationship study of SHP2 inhibitor containing 3,4,6-trihydroxy-5-oxo-5H-benzo[7]annulene.

  2019cited by this paper
• CuSO4/sodium ascorbate catalysed synthesis of benzosuberone and 1,2,3-triazole conjugates: Design, synthesis and in vitro anti-proliferative activity

  2019cited by this paper
• Dibenzepinones, dibenzoxepines and benzosuberones based p38α MAP kinase inhibitors: Their pharmacophore modelling, 3D-QSAR and docking studies

  2019cited by this paper
• Novel benzosuberone conjugates as potential anti-proliferative agents: Design, synthesis and molecular docking studies

  2019cited by this paper
• Cyclin-Dependent Kinase 2 Inhibitors in Cancer Therapy: An Update.

  2018cited by this paper
• A correlation study of biological activity and molecular docking of Asp and Glu linked bis-hydrazones of quinazolinones

  2018cited by this paper
• Selective inhibition of leukemia-associated SHP2E69K mutant by the allosteric SHP2 inhibitor SHP099

  2018cited by this paper
• Design of Aminopeptidase N Inhibitors as Anti-cancer Agents.

  2018cited by this paper
• Biological evaluation of benzosuberones

  2018cited by this paper
• Role and targeting of anaplastic lymphoma kinase in cancer

  2018cited by this paper
• Tamoxifen a pioneering drug: An update on the therapeutic potential of tamoxifen derivatives.

  2018cited by this paper
• Molecular Imaging of Aminopeptidase N in Cancer and Angiogenesis

  2018cited by this paper
• Characterization of Cnidoscolus quercifolius Pohl bark root extract and evaluation of cytotoxic effect on human tumor cell lines

  2018cited by this paper
• Novel Selective Estrogen Receptor Downregulators (SERDs) Developed against Treatment-Resistant Breast Cancer.

  2017cited by this paper
• Selective inhibition of PfA-M1, over PfA-M17, by an amino-benzosuberone derivative blocks malaria parasites development in vitro and in vivo

  2017cited by this paper
• Design of KDM4 Inhibitors with Antiproliferative Effects in Cancer Models.

  2017cited by this paper
• A novel piperazine linked β-amino alcohols bearing a benzosuberone scaffolds as anti-proliferative agents.

  2017cited by this paper
• Producing irreversible topoisomerase II-mediated DNA breaks by site-specific Pt(II)-methionine coordination chemistry

  2017cited by this paper
• Insight into the remarkable affinity and selectivity of the aminobenzosuberone scaffold for the M1 aminopeptidases family based on structure analysis

  2017cited by this paper
• Targeting Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MAPKAPK2, MK2): Medicinal Chemistry Efforts To Lead Small Molecule Inhibitors to Clinical Trials.

  2016cited by this paper
• Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

  2016cited by this paper
• Hydrazonoyl Halides as Precursors for Synthesis of Bioactive Thiazole and Thiadiazole Derivatives: Synthesis, Molecular Docking and Pharmacological Study

  2016cited by this paper
• Structures of a diverse set of colchicine binding site inhibitors in complex with tubulin provide a rationale for drug discovery

  2016cited by this paper
• A convenient synthesis and screening of benzosuberone bearing 1,2,3-triazoles against Mycobacterium tuberculosis.

  2016cited by this paper
• Role of Molecular Dynamics and Related Methods in Drug Discovery.

  2016cited by this paper
• Myo9b is a key player in SLIT/ROBO-mediated lung tumor suppression.

  2015cited by this paper
• The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities

  2015cited by this paper
• Small-molecule library screening by docking with PyRx.

  2015cited by this paper
• Binding of DNA-Intercalating Agents to Oxidized and Reduced Quinone Reductase 2.

  2015cited by this paper
• Structural interrogation of benzosuberene-based inhibitors of tubulin polymerization.

  2015cited by this paper
• DOCK 6: Impact of new features and current docking performance

  2015cited by this paper
• Targeting Cyclin-Dependent Kinases in Human Cancers: From Small Molecules to Peptide Inhibitors

  2015cited by this paper
• Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications

  2014cited by this paper
• Novel Tubulin Antagonist Pretubulysin Displays Antivascular Properties In Vitro and In Vivo

  2014cited by this paper
• Influence of the Length and Positioning of the Antiestrogenic Side Chain of Endoxifen and 4-Hydroxytamoxifen on Gene Activation and Growth of Estrogen Receptor Positive Cancer Cells

  2014cited by this paper
• HER2 in Breast Cancer: A Review and Update

  2014cited by this paper
• Cyclin-dependent kinases

  2014cited by this paper
• Recent advances in small organic molecules as DNA intercalating agents: synthesis, activity, and modeling.

  2014cited by this paper
• New cytotoxic benzosuberene analogs. Synthesis, molecular modeling and biological evaluation.

  2013cited by this paper
• Role of p38 MAP Kinase Signal Transduction in Solid Tumors.

  2013cited by this paper
• Rapid and efficient synthesis of a novel series of substituted aminobenzosuberone derivatives as potent, selective, non-peptidic neutral aminopeptidase inhibitors.

  2012cited by this paper
• Design and synthesis of pyrrolo[3,2-d]pyrimidine human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) dual inhibitors: exploration of novel back-pocket binders.

  2012cited by this paper
• Targeting the hinge glycine flip and the activation loop: novel approach to potent p38α inhibitors.

  2012cited by this paper
• Synthesis of 3-methoxy-9-(3,4,5-trimethoxyphenyl)-6,7-dihydro-5H-benzo[7]annulen-4-ol, a potent antineoplastic benzosuberene derivative for anti-cancer chemotherapy

  2012cited by this paper
• An Amino-Benzosuberene Analogue That Inhibits Tubulin Assembly and Demonstrates Remarkable Cytotoxicity.

  2012cited by this paper
• Discovery of an orally efficacious inhibitor of anaplastic lymphoma kinase.

  2012cited by this paper
• Surflex-Dock: Docking benchmarks and real-world application

  2012cited by this paper
• Naturally occurring himachalenes to benzocycloheptene amino vinyl bromide derivatives: as antidepressant molecules

  2012cited by this paper
• Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases

  2011cited by this paper
• A perspective on vascular disrupting agents that interact with tubulin: preclinical tumor imaging and biological assessment.

  2011cited by this paper
• HER2: biology, detection, and clinical implications.

  2011cited by this paper
• Discovery of a potent inhibitor of anaplastic lymphoma kinase with in vivo antitumor activity.

  2010cited by this paper
• In vivo and in vitro SAR of tetracyclic MAPKAP-K2 (MK2) inhibitors. Part II.

  2010cited by this paper
• Crystal structures of anaplastic lymphoma kinase in complex with ATP competitive inhibitors.

  2010cited by this paper
• AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading

  2009cited by this paper
• Colchicine update: 2008.

  2009cited by this paper
• Synthesis, tautomerism, and antimicrobial, anti-HCV, anti-SSPE, antioxidant, and antitumor activities of arylazobenzosuberones.

  2009cited by this paper
• Synthesis, Modelling, and Antimitotic Properties of Tricyclic Systems Characterised by a 2‐(5‐Phenyl‐1H‐pyrrol‐3‐yl)‐1,3,4‐oxadiazole Moiety

  2009cited by this paper

• A comparison of honeybee and scorpion venoms as anticancer agents against three different cancer cell lines: lung, colon, and breast cancer

  2026cites this paper
• Molecular Docking and Target‐Specific Binding Profiles of Benzosuberane‐Based Compounds

  2025cites this paper
• Design, Synthesis, Characterization and Molecular Docking Evaluation of Dual-Imino Benzopyran Analogues as Potential VEGFR2 and EGFR Inhibitors for Breast Cancer Therapy

  2025cites this paper