Abstract
The search for newer histone deacetylase (HDAC) inhibitors has attracted a great deal of interest of medicinal chemists worldwide, especially after the first HDAC inhibitor (Zolinza®, widely known as SAHA or Suberoylanilide hydroxamic acid) was approved by the FDA for the treatment of Tcell lymphoma in 2006. As a continuity of our ongoing research in this area, we designed and synthesized a series of 5-aryl-1,3,4-thiadiazole-based hydroxamic acids as analogues of SAHA and evaluated their biological activities. Most of the compounds in this series, e.g. compounds with 5-aryl moiety being 2- furfuryl (5a), 5-bromofuran-2-yl (5b), 5-methylfuran-2-yl (5c), thiophen-2-yl (5d), 5-methylthiophen-2-yl (5f) and pyridyl (5g-i), were found to have potent anticancer cytotoxicity with IC50 values of generally 5- to 10-fold lower than that of SAHA in 4 human cancer cell lines assayed. Those compounds with potent cytotoxicity were also found to have strong HDAC inhibition effects. Docking studies revealed that compounds 5a and 5d displayed high affinities towards HDAC2 and 8.
Keywords: Histone deacetylase (HDAC) inhibitors, 5-aryl-1, 3, 4-thiadiazole, cytotoxicity, heterocycle.
Medicinal Chemistry
Title:5-Aryl-1,3,4-Thiadiazole-Based Hydroxamic Acids as Histone Deacetylase Inhibitors and Antitumor Agents: Synthesis, Bioevaluation and Docking Study
Volume: 11 Issue: 3
Author(s): Tran Thi Lan Huong, Do Thi Mai Dung, Dao Thi Kim Oanh, Tran Thi Bich Lan, Phan Thi Phuong Dung, Vu Duc Loi, Kyung Rok Kim, Byung Woo Han, Jieun Yun, Jong Soon Kang, Youngsoo Kim, Sang-Bae Han and Nguyen-Hai Nam
Affiliation:
Keywords: Histone deacetylase (HDAC) inhibitors, 5-aryl-1, 3, 4-thiadiazole, cytotoxicity, heterocycle.
Abstract: The search for newer histone deacetylase (HDAC) inhibitors has attracted a great deal of interest of medicinal chemists worldwide, especially after the first HDAC inhibitor (Zolinza®, widely known as SAHA or Suberoylanilide hydroxamic acid) was approved by the FDA for the treatment of Tcell lymphoma in 2006. As a continuity of our ongoing research in this area, we designed and synthesized a series of 5-aryl-1,3,4-thiadiazole-based hydroxamic acids as analogues of SAHA and evaluated their biological activities. Most of the compounds in this series, e.g. compounds with 5-aryl moiety being 2- furfuryl (5a), 5-bromofuran-2-yl (5b), 5-methylfuran-2-yl (5c), thiophen-2-yl (5d), 5-methylthiophen-2-yl (5f) and pyridyl (5g-i), were found to have potent anticancer cytotoxicity with IC50 values of generally 5- to 10-fold lower than that of SAHA in 4 human cancer cell lines assayed. Those compounds with potent cytotoxicity were also found to have strong HDAC inhibition effects. Docking studies revealed that compounds 5a and 5d displayed high affinities towards HDAC2 and 8.
Export Options
About this article
Cite this article as:
Huong Thi Lan Tran, Dung Thi Mai Do, Oanh Thi Kim Dao, Lan Thi Bich Tran, Dung Thi Phuong Phan, Loi Vu Duc, Kim Rok Kyung, Han Woo Byung, Yun Jieun, Kang Soon Jong, Kim Youngsoo, Han Sang-Bae and Nam Nguyen-Hai, 5-Aryl-1,3,4-Thiadiazole-Based Hydroxamic Acids as Histone Deacetylase Inhibitors and Antitumor Agents: Synthesis, Bioevaluation and Docking Study , Medicinal Chemistry 2015; 11 (3) . https://dx.doi.org/10.2174/1573406410666140925153128
DOI https://dx.doi.org/10.2174/1573406410666140925153128 |
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
-
Medium-Term Culture of Primary Oral Squamous Cell Carcinoma in a Three- Dimensional Model: Effects on Cell Survival Following Topical 5-Fluororacile Delivery by Drug-Loaded Matrix Tablets
Current Pharmaceutical Design Therapeutic Applications of Crocus sativus L. (Saffron): A Review
The Natural Products Journal Toll-Like Receptors: Cost or Benefit for Cancer?
Current Pharmaceutical Design The Mechanism of Calcitriol in Cancer Prevention and Treatment
Current Medicinal Chemistry Medium-term Culture of Normal Human Oral Mucosa: A Novel Three-dimensional Model to Study the Effectiveness of Drugs Administration
Current Pharmaceutical Design Remote Preconditioning- Endocrine Factors in Organ Protection Against Ischemic Injury
Endocrine, Metabolic & Immune Disorders - Drug Targets Bradykinin Antagonists as Anti-Cancer Agents
Current Pharmaceutical Design Recent Progress on Apoptotic Activity of Triazoles
Current Drug Targets Editorial [Hot Topic: Targeted Therapies for Pancreatic Cancer Executive (Guest Editor: Qingyong Ma)]
Current Pharmaceutical Design Potential Applications of <i>Sarcopoterium Spinosum</i> as Medicinal Plants: Overview and Future Trends
Current Traditional Medicine Hydrodynamic Gene Delivery to the Liver: Theoretical and Practical Issues for Clinical Application
Current Gene Therapy New Insight into P-Glycoprotein as a Drug Target
Anti-Cancer Agents in Medicinal Chemistry Overcoming the Challenges of siRNA Delivery: Nanoparticle Strategies
Current Drug Delivery Alpha-Crystallins and Tumorigenesis
Current Molecular Medicine Recent Advances in Research on the Most Novel Carbonic Anhydrases,CA XIII and XV
Current Pharmaceutical Design The Potential for Dietary Modification of Islet β-Cell Homeostasis in Autoimmune Diabetes
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Potent Chemopreventive Agents Against Pancreatic Cancer
Current Cancer Drug Targets Patent Annotations
Recent Patents on Anti-Cancer Drug Discovery Recent Advances on the Development of Pharmacotherapeutic Agents on the Basis of Human Serum Albumin
Current Pharmaceutical Design Molecular Chaperone ORP150 in ER Stress–related Diseases
Current Pharmaceutical Design