Abstract
Many cancer cells are known to have defects in the apoptosis machinery. Therefore identification of compounds that can activate or promote apoptosis in cancer cells is an attractive approach for targeted therapies. By applying a novel cell- and caspase-based Anti-cancer Screening Apoptosis Program (ASAP) HTS assay, 4-aryl-4H-chromenes were identified as potent apoptosis inducers. 4- Aryl-4H-chromenes were found to induce nuclear fragmentation and PARP cleavage, as well as to arrest cells at the G2/M stage followed by apoptosis as determined by the flow cytometry analysis assay in multiple human cell lines (e.g. Jurkat, T47D). These compounds were found to be highly active in the growth inhibition MTT assay, including for paclitaxel resistant, p-glycoprotein overexpressed, MESSA/ DX5 tumor cells. Functionally, they were found to be potent inhibitors of tubulin polymerization and to effectively inhibit the binding of colchicine to tubulin. In addition, several 4-aryl-4H-chromenes were also found to be effective vascular disrupting agents (VDA). One of the lead compounds, EPC2407, is currently in clinical trials as a novel tumor vascular disrupting agent.
Keywords: Apoptosis inducers, HTS assay, anti-cancer drug, SAR studies, tubulin inhibitors, vascular disrupting agent (VDA)
Anti-Cancer Agents in Medicinal Chemistry
Title: Discovery of 4-Aryl-4H-Chromenes as Potent Apoptosis Inducers Using a Cell- and Caspase-Based Anti-Cancer Screening Apoptosis Program (ASAP): SAR Studies and the Identification of Novel Vascular Disrupting Agents
Volume: 9 Issue: 4
Author(s): Sui Xiong Cai, John Drewe and William Kemnitzer
Affiliation:
Keywords: Apoptosis inducers, HTS assay, anti-cancer drug, SAR studies, tubulin inhibitors, vascular disrupting agent (VDA)
Abstract: Many cancer cells are known to have defects in the apoptosis machinery. Therefore identification of compounds that can activate or promote apoptosis in cancer cells is an attractive approach for targeted therapies. By applying a novel cell- and caspase-based Anti-cancer Screening Apoptosis Program (ASAP) HTS assay, 4-aryl-4H-chromenes were identified as potent apoptosis inducers. 4- Aryl-4H-chromenes were found to induce nuclear fragmentation and PARP cleavage, as well as to arrest cells at the G2/M stage followed by apoptosis as determined by the flow cytometry analysis assay in multiple human cell lines (e.g. Jurkat, T47D). These compounds were found to be highly active in the growth inhibition MTT assay, including for paclitaxel resistant, p-glycoprotein overexpressed, MESSA/ DX5 tumor cells. Functionally, they were found to be potent inhibitors of tubulin polymerization and to effectively inhibit the binding of colchicine to tubulin. In addition, several 4-aryl-4H-chromenes were also found to be effective vascular disrupting agents (VDA). One of the lead compounds, EPC2407, is currently in clinical trials as a novel tumor vascular disrupting agent.
Export Options
About this article
Cite this article as:
Cai Xiong Sui, Drewe John and Kemnitzer William, Discovery of 4-Aryl-4H-Chromenes as Potent Apoptosis Inducers Using a Cell- and Caspase-Based Anti-Cancer Screening Apoptosis Program (ASAP): SAR Studies and the Identification of Novel Vascular Disrupting Agents, Anti-Cancer Agents in Medicinal Chemistry 2009; 9 (4) . https://dx.doi.org/10.2174/1871520610909040437
DOI https://dx.doi.org/10.2174/1871520610909040437 |
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
Rechallenge Therapy in different types of cancer
Cancer is responsible for approximately 8 million deaths annually all worldwide. The Global burden of cancer (GLOBOCAN) 2020 reported 19.3 million new cases of cancer, which is projected to increase to 28.4 million by 2040.In the future , female breast cancer will be the most common cancer (11.7%) followed by ...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
-
Medicinal Chemistry of the Epigenetic Diet and Caloric Restriction
Current Medicinal Chemistry Calorie Restriction and Dietary Restriction Mimetics: A Strategy for Improving Healthy Aging and Longevity
Current Pharmaceutical Design Synthesis and Altered Biodistribution of 99mTc Labeled Vincristine in Animal Model
Current Medical Imaging MicroRNA Therapeutics: The Emerging Anticancer Strategies
Recent Patents on Anti-Cancer Drug Discovery Drug-Related Cardiotoxicity for the Treatment of Haematological Malignancies in Elderly
Current Pharmaceutical Design Recent Advances in PUVA Photochemotherapy and PDT for the Treatment of Cancer
Current Pharmaceutical Design An Overall Picture of Chemokine Receptors: Basic Research and Drug Development
Current Pharmaceutical Design Vaccines and Vaccine Strategies Against HIV
Current Drug Targets Monoterpenes as Perspective to Chronic Pain Management: A Systematic Review
Current Drug Targets A Review on Natural Sources Derived Protein Nanoparticles as Anticancer Agents
Current Topics in Medicinal Chemistry T Cell Replicative Senescence in Human Aging
Current Pharmaceutical Design Recent Developments in Pleuromutilin Derivatives: A Promising Class Against Bacterial Respiratory Disease
Current Respiratory Medicine Reviews Developments in the Application of 1,2,3-Triazoles in Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery Neurotrophic Factor Treatment After Spinal Root Avulsion Injury
Central Nervous System Agents in Medicinal Chemistry Role of miR-193a in Cancer: Complexity and Factors Control the Pattern of its Expression
Current Cancer Drug Targets Bleomycin and its Role in Inducing Apoptosis and Senescence in Lung Cells - Modulating Effects of Caveolin-1
Current Cancer Drug Targets Role of Cathepsin K in Normal Joints and in the Development of Arthritis
Current Drug Targets Advances in Regulating Tumorigenicity and Metastasis of Cancer Through TrkB Signaling
Current Cancer Drug Targets An Insight into Drug Repositioning for the Development of Novel Anti-Cancer Drugs
Current Topics in Medicinal Chemistry Antitumoral-Lipid-Based Nanoparticles: a Platform for Future Application in Osteosarcoma therapy
Current Pharmaceutical Design