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.

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.

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.0K
Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists01:29

Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists

Dopamine receptor antagonists, also known as antipsychotic agents, are critical in managing chemotherapy-induced vomiting. These antiemetic agents block dopamine receptors in the chemoreceptor trigger zone (CTZ), inhibiting signal transmission to the vomiting center. Antipsychotic agents encompass phenothiazines (PTZ), butyrophenones, benzamides, and thienobenzodiazepines (Zyprexa), which are utilized for their antiemetic and sedative properties.
Phenothiazines, such as prochlorperazine...
492
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.1K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.9K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.2K
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists01:27

Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists

5-HT3 receptor antagonists, such as dolasetron, granisetron (Kytril), ondansetron (Zofran), and palonosetron (Axoli), are crucial in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea. These drugs selectively block 5-HT3 receptors in the visceral vagal and spinal afferent nerves, chemoreceptor trigger zone, and the vomiting center. They have a rapid onset of action and can be given as a single dose before chemotherapy. Ondansetron and granisetron, in particular,...
347