Abstract
Results from clinical studies have demonstrated that inhibitors of histone deacetylase (HDAC) enzymes possess promise for the treatment of several types of cancer. Zolinza® (widely known as SAHA) has been approved by the FDA for the treatment of T-cell lymphoma. As a continuity of our ongoing research to find novel small molecules to target these important enzymes, we synthesized a series of benzothiazole-containing analogues of SAHA and found several compounds with very potent anticancer cytotoxicity. In this study, three more compounds of this type, including N1-(6- chlorobenzo[d]thiazol-2-yl)-N8-hydroxyoctanediamide (3a), N1-[6-(trifluoromethyl)benzo[d]thiazol-2-yl]-N8-hydroxyoctanediamide (3b) and N1-(thiazol-2-yl)-N8-hydroxyoctanediamide (6) were synthesized and evaluated for HDAC inhibition and cytotoxic activities. All three compounds showed very potent HDAC inhibitory effects. Docking revealed that both two compounds 3a, 3b showed higher affinities towards HDAC8 compared to SAHA. In vitro, compound 3a exhibited cytotoxicity equipotent to SAHA against five human cancer cell lines. In term of in vivo activity, compound 3a demonstrated equivalent efficacy to SAHA in mouse xenograft model.
Keywords: Histone deacetylase inhibitors, benzothiazole, heterocycle.
Medicinal Chemistry
Title:New Benzothiazole/thiazole-Containing Hydroxamic Acids as Potent Histone Deacetylase Inhibitors and Antitumor Agents
Volume: 9 Issue: 8
Author(s): Truong Thanh Tung, Dao Thi Kim Oanh, Phan Thi Phuong Dung, Van Thi My Hue, Sang Ho Park, Byung Woo Han, Youngsoo Kim, Jin-Tae Hong, Sang-Bae Han and Nguyen-Hai Nam
Affiliation:
Keywords: Histone deacetylase inhibitors, benzothiazole, heterocycle.
Abstract: Results from clinical studies have demonstrated that inhibitors of histone deacetylase (HDAC) enzymes possess promise for the treatment of several types of cancer. Zolinza® (widely known as SAHA) has been approved by the FDA for the treatment of T-cell lymphoma. As a continuity of our ongoing research to find novel small molecules to target these important enzymes, we synthesized a series of benzothiazole-containing analogues of SAHA and found several compounds with very potent anticancer cytotoxicity. In this study, three more compounds of this type, including N1-(6- chlorobenzo[d]thiazol-2-yl)-N8-hydroxyoctanediamide (3a), N1-[6-(trifluoromethyl)benzo[d]thiazol-2-yl]-N8-hydroxyoctanediamide (3b) and N1-(thiazol-2-yl)-N8-hydroxyoctanediamide (6) were synthesized and evaluated for HDAC inhibition and cytotoxic activities. All three compounds showed very potent HDAC inhibitory effects. Docking revealed that both two compounds 3a, 3b showed higher affinities towards HDAC8 compared to SAHA. In vitro, compound 3a exhibited cytotoxicity equipotent to SAHA against five human cancer cell lines. In term of in vivo activity, compound 3a demonstrated equivalent efficacy to SAHA in mouse xenograft model.
Export Options
About this article
Cite this article as:
Tung Thanh Truong, Kim Oanh Thi Dao, Phuong Dung Thi Phan, My Hue Thi Van, Park Ho Sang, Han Woo Byung, Kim Youngsoo, Hong Jin-Tae, Han Sang-Bae and Nam Nguyen-Hai, New Benzothiazole/thiazole-Containing Hydroxamic Acids as Potent Histone Deacetylase Inhibitors and Antitumor Agents, Medicinal Chemistry 2013; 9 (8) . https://dx.doi.org/10.2174/15734064113099990027
DOI https://dx.doi.org/10.2174/15734064113099990027 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...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
-
Drugs for AIDS
Mini-Reviews in Medicinal Chemistry The Anticancer Properties of Dietary Polyphenols and its Relation with Apoptosis
Current Pharmaceutical Design Omalizumab for Asthma: Indications, Off-Label Uses and Future Directions
Recent Patents on Inflammation & Allergy Drug Discovery Retinal Ganglion Cell Gene Therapy and Visual System Repair
Current Gene Therapy The Role of Protein Kinase C-alpha (PKC-α) in Cancer and its Modulation by the Novel PKC-α-Specific Inhibitor Aprinocarsen
Current Pharmaceutical Design Molecular Targets for the Treatment of Testicular Germ Cell Tumors
Mini-Reviews in Medicinal Chemistry Immune Restoration Disease: A Consequence of Dysregulated Immune Responses After HAART
Current HIV Research Will Antirheumatic Treatment Improve Cardiovascular Outcomes in Patients with Rheumatoid Arthritis?
Current Pharmaceutical Design Evaluation of Vitamin C as a Personalized Adjuvant Medicine: Pharmacogenomic Studies
Current Pharmacogenomics and Personalized Medicine Mucosal T Cell Proliferation and Apoptosis in Inflammatory Bowel Disease
Current Drug Targets Cancer and Aids: New Trends in Drug Design and Chemotherapy
Current Computer-Aided Drug Design Neddylation Pathway as a Novel Anti-cancer Target: Mechanistic Investigation and Therapeutic Implication
Anti-Cancer Agents in Medicinal Chemistry Older and New Formulations of Cladribine. Pharmacology and Clinical Efficacy in Hematological Malignancies
Recent Patents on Anti-Cancer Drug Discovery Transcriptional Regulation of the p53 Tumor Suppressor Gene: A Potential Target for Cancer Therapeutics?
Recent Patents on DNA & Gene Sequences Chemical Diversity and Bioactivity of Marine Sponges of the Genus Oceanapia: A Review
Mini-Reviews in Organic Chemistry Role of Hsp70 in Cancer Growth and Survival
Protein & Peptide Letters Can Dietary Antioxidants Reduce the Incidence of Brain Tumors?
Current Drug Metabolism Network Medicine and High Throughput Screening
Current Drug Discovery Technologies Advances in Photodynamic Therapy Assisted by Electroporation
Current Drug Metabolism Too Much of a Good Thing: Suicide Prevention Promotes Chemoresistance in Ovarian Carcinoma
Current Cancer Drug Targets