Abstract
The utility of natural products for identifying anticancer agents has been highly pursued in the last decades and over 100 drug molecules in clinic are natural products or natural product-derived compounds. Natural products are believed to be able to cover unexplored chemical space that is normally not occupied by commercially available molecule libraries. However, the low abundance and synthetic intractability of natural products have limited their applications in drug discovery. Recently, the identification of biologically relevant fragments derived from biologically validated natural products has been recognized as a powerful strategy in searching new biological probes and drugs. The spirocyclic oxindoles, as privileged structural scaffolds, have shown their potential in designing new drugs. Several anticancer drug candidates such as SAR405838, RO8994, CFI-400945 and their bioisosteres are undergoing clinical trials or preclinical studies. To highlight the significant progress, we focus on illustrating the discovery of SAR405838, RO8994, CFI-400945 and their bioisosteres for cancer therapy using substructure-based strategies and discussing modes of action, binding models and preclinical data.
Keywords: Anticancer agents, cancer therapy, MDM2 inhibitors, natural products, PLK4 inhibitors, spirooxindoles.
Anti-Cancer Agents in Medicinal Chemistry
Title:Natural Product-Derived Spirooxindole Fragments Serve as Privileged Substructures for Discovery of New Anticancer Agents
Volume: 16 Issue: 10
Author(s): Bin Yu, Yi-Chao Zheng, Xiao-Jing Shi, Ping-Ping Qi and Hong-Min Liu
Affiliation:
Keywords: Anticancer agents, cancer therapy, MDM2 inhibitors, natural products, PLK4 inhibitors, spirooxindoles.
Abstract: The utility of natural products for identifying anticancer agents has been highly pursued in the last decades and over 100 drug molecules in clinic are natural products or natural product-derived compounds. Natural products are believed to be able to cover unexplored chemical space that is normally not occupied by commercially available molecule libraries. However, the low abundance and synthetic intractability of natural products have limited their applications in drug discovery. Recently, the identification of biologically relevant fragments derived from biologically validated natural products has been recognized as a powerful strategy in searching new biological probes and drugs. The spirocyclic oxindoles, as privileged structural scaffolds, have shown their potential in designing new drugs. Several anticancer drug candidates such as SAR405838, RO8994, CFI-400945 and their bioisosteres are undergoing clinical trials or preclinical studies. To highlight the significant progress, we focus on illustrating the discovery of SAR405838, RO8994, CFI-400945 and their bioisosteres for cancer therapy using substructure-based strategies and discussing modes of action, binding models and preclinical data.
Export Options
About this article
Cite this article as:
Yu Bin, Zheng Yi-Chao, Shi Xiao-Jing, Qi Ping-Ping and Liu Hong-Min, Natural Product-Derived Spirooxindole Fragments Serve as Privileged Substructures for Discovery of New Anticancer Agents, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (10) . https://dx.doi.org/10.2174/1871520615666151102093825
DOI https://dx.doi.org/10.2174/1871520615666151102093825 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Discovery of Lead compounds targeting transcriptional regulation
Transcriptional regulation plays key physiological functions in body growth and development. Transcriptional dysregulation is one of important biomarkers of tumor genesis and progression, which is involved in regulating tumor cell processes such as cell proliferation, differentiation, and apoptosis. Additionally, it plays a pivotal role in angiogenesis and promotes tumor metastasis ...read more
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Innovative targets in medicinal chemistry
Medicinal chemistry continuously evolves in response to emerging healthcare needs and advancements in scientific understanding. This special issue explores the current landscape of innovative targets in medicinal chemistry, highlighting the quest for novel therapeutic avenues. From traditional drug targets such as enzymes and receptors to emerging targets like protein-protein interactions ...read more
Metalloenzymes and Cancer: Μetalloenzyme Ιnhibitors and Artificial Metalloenzymes as anti-cancer agents
Metalloenzymes are enzymes containing metal ions, which are directly bound to the enzyme and play a role in promoting catalysis. About one-third of all enzymes known so far are metalloenzymes [1]. Metalloenzymes are central to a wide range of essential biological activities, including nucleic acid modification, protein degradation, and many ...read more
![](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Synthesis and Urease Inhibitory Activity of Some 5-Aminomethylene Barbituric/Thiobarbituric Acid Derivatives
Letters in Drug Design & Discovery Molecular Aspects of Resistance to Biological and Non-Biological Drugs and Strategies to Overcome Resistance in Colorectal Cancer
Current Medicinal Chemistry A Novel Bromomelatonin Derivative Suppresses Apoptosis with Regulating the Expression of Bcl-2 Family Genes
Letters in Drug Design & Discovery Molecule of the Month
Current Topics in Medicinal Chemistry Quantifying Risk: The Role of Absolute and Relative Measures in Interpreting Risk of Adverse Reactions from Product Labels of Antipsychotic Medications
Current Drug Safety Induction of Tumour Cell Senescence: A New Strategy in Anticancer Treatment
Medicinal Chemistry Reviews - Online (Discontinued) The Scatter Factor Signaling Pathways as Therapeutic Associated Target in Cancer Treatment
Current Medicinal Chemistry Crude Methanol Extract of Rosin Gum Exhibits Specific Cytotoxicity against Human Breast Cancer Cells via Apoptosis Induction
Anti-Cancer Agents in Medicinal Chemistry Current Development of Metal Complexes with Diamine Ligands as Potential Anticancer Agents
Current Medicinal Chemistry Intercellular Crosstalk Via Extracellular Vesicles in Tumor Milieu as Emerging Therapies for Cancer Progression
Current Pharmaceutical Design The Role of the Complex USP1/WDR48 in Differentiation and Proliferation Processes in Cancer Stem Cells
Current Stem Cell Research & Therapy <i>Echinococcus granulosus</i> as a Promising Therapeutic Agent against Triplenegative Breast Cancer
Current Cancer Therapy Reviews A Novel Probiotic Formula, BIOCG, Protects Against Alzheimer’s-Related Cognitive Deficits via Regulation of Dendritic Spine Dynamics
Current Alzheimer Research TRAIL-Based Therapeutic Approaches for the Treatment of Pediatric Malignancies
Current Medicinal Chemistry Preface
Anti-Cancer Agents in Medicinal Chemistry Dynamic Changes in Phenotypic Groups in Patients with Stable Angina Pectoris after Treatment with Xinxuekang Capsule: A Randomized Controlled Trial
Current Vascular Pharmacology Secretory Leukocyte Protease Inhibitor: More than Just A Protease Inhibitor
Current Immunology Reviews (Discontinued) Synergistic Interactions between GW8510 and Gemcitabine in an In Vitro Model of Pancreatic Cancer
Anti-Cancer Agents in Medicinal Chemistry Gut Inflammation in Response to Injury: Potential Target for Therapeutic Intervention
Recent Patents on Anti-Infective Drug Discovery Interleukin 10 in Antiviral Responses
Current Immunology Reviews (Discontinued)