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
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
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- 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
-
Editorial: [Hot Topic: Antidotes and Rescue Therapies]
Current Pharmaceutical Biotechnology Preparation and Surface Modification of Polymeric Nanoparticles for Drug Delivery: State of the Art
Recent Patents on Drug Delivery & Formulation Functions of S100 Proteins
Current Molecular Medicine Bryostatin-1 Synergizes with Histone Deacetylase Inhibitors to Reactivate HIV-1 from Latency
Current HIV Research Gold Nanoparticles - Synthesis and Applications in Cancer Management
Recent Patents on Materials Science Animal Venoms have Potential to Treat Cancer
Current Topics in Medicinal Chemistry How and Why to Screen for CYP2D6 Interindividual Variability in Patients Under Pharmacological Treatments
Current Drug Metabolism Cytotoxicity of Hydrazones of Morpholine Bearing Mannich Bases Towards Huh7 and T47D Cell Lines and Their Effects on Mitochondrial Respiration
Letters in Drug Design & Discovery Untapped Potential of Disordered Proteins in Current Druggable Human Proteome
Current Drug Targets PI3K/Akt/mTOR Pathway Inhibitors in Cancer: A Perspective on Clinical Progress
Current Medicinal Chemistry Molecular Mechanisms of Anti-cancer Activities of β-elemene: Targeting Hallmarks of Cancer
Anti-Cancer Agents in Medicinal Chemistry Energetic Metabolic Roles in Pulmonary Arterial Hypertension and Right Ventricular Remodeling
Current Pharmaceutical Design Using Biologic Agents in Pediatric Rheumatologic Diseases
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Plasminogen Activator System and Vascular Disease
Current Vascular Pharmacology L-Sulforaphane Confers Protection Against Oxidative Stress in an In Vitro Model of Age-Related Macular Degeneration
Current Molecular Pharmacology Investigation of New Phenothiazine and Carbazole Derivatives as Potential Inhibitors of Human Farnesyltransferase
Letters in Drug Design & Discovery Evaluation of Melatonin Effect on Human Breast Cancer Stem Cells Using a Threedimensional Growth Method of Mammospheres
Anti-Cancer Agents in Medicinal Chemistry MYC as Therapeutic Target for Embryonal Tumors: Potential and Challenges
Current Cancer Drug Targets Micro-/Nano-Scale Biointerfaces, Mechanical Coupling and Cancer Therapy
Current Topics in Medicinal Chemistry Influence of Aldo-keto Reductase 1C3 in Prostate Cancer - A Mini Review
Current Cancer Drug Targets