Abstract
Histone deacetylases (HDACs) inhibitors have multiple effects targeting the cancer cells and have become one of the promising cancer therapeutics with possibly broad applicability. Combination of HDAC inhibitors with the cytotoxic fluorouracil (5-FU) showed additive and synergistic effects both in vitro and in vivo. To explore the possibility in cancer therapy of a bivalent agent that combines two bioactive groups within a single molecular architecture, we designed and synthesized new dual-acting compounds by combining the bioactive fragment of MS-275, a clinical HDACs inhibitor, with cytotoxic agent 5-FU. The target compounds 9a and 9b showed comparable HDACs inhibition with MS-275 and moderate antiproliferative acitivities against six cancer cells lines.
Keywords: Anticancer, HDAC, MS-275, Multitarget, 5-Fluorouracil.
Medicinal Chemistry
Title:Discovery of Multi-target Anticancer Agents Based on HDAC Inhibitor MS-275 and 5-FU
Volume: 12 Issue: 1
Author(s): Yuqi Jiang, Xiaoguang Li, Xiaoyang Li, Jinning Hou, Yongzheng Ding, Jian Zhang, Wenfang Xu and Yingjie Zhang
Affiliation:
Keywords: Anticancer, HDAC, MS-275, Multitarget, 5-Fluorouracil.
Abstract: Histone deacetylases (HDACs) inhibitors have multiple effects targeting the cancer cells and have become one of the promising cancer therapeutics with possibly broad applicability. Combination of HDAC inhibitors with the cytotoxic fluorouracil (5-FU) showed additive and synergistic effects both in vitro and in vivo. To explore the possibility in cancer therapy of a bivalent agent that combines two bioactive groups within a single molecular architecture, we designed and synthesized new dual-acting compounds by combining the bioactive fragment of MS-275, a clinical HDACs inhibitor, with cytotoxic agent 5-FU. The target compounds 9a and 9b showed comparable HDACs inhibition with MS-275 and moderate antiproliferative acitivities against six cancer cells lines.
Export Options
About this article
Cite this article as:
Jiang Yuqi, Li Xiaoguang, Li Xiaoyang, Hou Jinning, Ding Yongzheng, Zhang Jian, Xu Wenfang and Zhang Yingjie, Discovery of Multi-target Anticancer Agents Based on HDAC Inhibitor MS-275 and 5-FU, Medicinal Chemistry 2016; 12 (1) . https://dx.doi.org/10.2174/1573406411666150714111045
DOI https://dx.doi.org/10.2174/1573406411666150714111045 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
- 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
-
From the Design to the Clinical Application of Thromboxane Modulators
Current Pharmaceutical Design JAK Inhibitors: Pharmacology and Clinical Activity in Chronic Myeloprolipherative Neoplasms
Current Medicinal Chemistry The Leukocyte Common Antigen-Related Protein LAR: Candidate PTP for Inhibitory Targeting
Current Topics in Medicinal Chemistry Genetics of Bladder Malignant Tumors in Childhood
Current Genomics Editorial [Hot topic: Selected New Developments in Oncology (Guest Editors: Jos H. Beijnen and Jan H.M. Schellens)]
Current Clinical Pharmacology Enhancement of the Antiproliferative Activity of Gemcitabine by Modulation of c-Met Pathway in Pancreatic Cancer
Current Pharmaceutical Design Editorial [Hot topic: New Generation Cancer Vaccines: From Tumor Immunology to Clinical Applications (Executive Editor: Simone Mocellin)]
Current Pharmaceutical Design Quasi-Life Self-Organizing Systems: Based on Ensembles of Succinylated Derivatives of Interferon-Gamma
Current Medicinal Chemistry Incidence of Profound Hypogammaglobulinemia and Infection Rate in Lymphoma Patients Following the Combination of Chemotherapy and Rituximab
Recent Patents on Anti-Cancer Drug Discovery Clozapine Induced Eosinophilia in a Case of Schizoaffective Disorder
Current Psychopharmacology Thiopurine Immunomodulators in Ulcerative Colitis: Moving Forward with Current Evidence
Current Drug Targets Fluoroquinolones Prophylaxis of Bacterial Infections in Neutropenic Patients: Time to Re-Evaluate
Current Cancer Therapy Reviews Antiproliferative and Proapoptotic Effects of Proteasome Inhibitors and their Combination with Histone Deacetylase Inhibitors on Leukemia Cells
Cardiovascular & Hematological Disorders-Drug Targets Disorders of Protein Biogenesis and Stability
Protein & Peptide Letters Cancer/Testis Antigens Trigger Epithelial-Mesenchymal Transition and Genesis of Cancer Stem-Like Cells
Current Pharmaceutical Design Controlled-release Particulate Cytokine Adjuvants for Cancer Therapy
Endocrine, Metabolic & Immune Disorders - Drug Targets Liposomal-All-trans-Retinoic Acid in the Treatment of Acute Promyelocytic Leukemia
Current Cancer Therapy Reviews Nutritional Support in Cancer
Current Nutrition & Food Science Endothelial Progenitor Cells: Quod Erat Demonstrandum?
Current Pharmaceutical Design Integrating Qualitative and Quantitative Tools for the Detection and Identification of Lectins in Major Human Diseases
Protein & Peptide Letters