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Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Quinazoline Based HDAC Dual Inhibitors as Potential Anti-Cancer Agents
Jyothi Dhuguru1, Ola A Ghoneim2
1Mitchell Cancer Institute, University of South Alabama, 1660 SpringHill Ave., Mobile, AL 36604, USA.
Abstract:
Cancer is the most devastating disease and second leading cause of death around the world. Despite scientific advancements in the diagnosis and treatment of cancer which can include targeted therapy, chemotherapy, endocrine therapy, immunotherapy, radiotherapy and surgery in some cases, cancer cells appear to outsmart and evade almost any method of treatment by developing drug resistance. Quinazolines are the most versatile, ubiquitous and privileged nitrogen bearing heterocyclic compounds with a wide array of biological and pharmacological applications. Most of the anti-cancer agents featuring quinazoline pharmacophore have shown promising therapeutic activity. Therefore, extensive research is underway to explore the potential of these privileged scaffolds. In this context, a molecular hybridization approach to develop hybrid drugs has become a popular tool in the field of drug discovery, especially after witnessing the successful results during the past decade. Histone deacetylases (HDACs) have emerged as an important anti-cancer target in the recent years given its role in cellular growth, gene regulation, and metabolism. Dual inhibitors, especially based on HDAC in particular, have become the center stage of current cancer drug development. Given the growing significance of dual HDAC inhibitors, in this review, we intend to compile the development of quinazoline based HDAC dual inhibitors as anti-cancer agents.
Insights
Cancer drug resistance is a major challenge. This review explores quinazoline-based dual histone deacetylase (HDAC) inhibitors as a promising strategy to overcome resistance and develop novel anti-cancer therapies.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Oncology
Background:
- Cancer remains a leading cause of death globally, with drug resistance limiting treatment efficacy.
- Quinazoline scaffolds are recognized for their diverse pharmacological properties and are integral to many anti-cancer agents.
- Histone deacetylases (HDACs) are crucial in cancer progression, making them significant therapeutic targets.
Purpose of the Study:
- To review the development of quinazoline-based dual histone deacetylase (HDAC) inhibitors.
- To highlight their potential as anti-cancer agents, particularly in overcoming drug resistance.
Main Methods:
- Literature review focusing on quinazoline derivatives and their dual HDAC inhibitory activity.
- Analysis of molecular hybridization strategies in drug discovery.
- Compilation of studies demonstrating anti-cancer effects of these compounds.
Main Results:
- Quinazoline-based compounds exhibit significant therapeutic potential against various cancers.
- Dual HDAC inhibitors show promise in circumventing drug resistance mechanisms.
- Molecular hybridization has successfully yielded potent anti-cancer drug candidates.
Conclusions:
- Quinazoline-based dual HDAC inhibitors represent a promising avenue for novel cancer therapy development.
- Further research into these hybrid molecules could lead to more effective treatments for drug-resistant cancers.
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