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Drugs that Destabilize Microtubules01:10

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Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
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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,...
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The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
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Drugs that Stabilize Microtubules01:15

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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...
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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.
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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...
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Imidazoles as Potential Anticancer Agents: An Update on Recent Studies.

Pankaj Sharma1, Chris LaRosa1, Janet Antwi2

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Imidazole derivatives are promising anticancer agents, targeting key proteins like kinases and PARP. This review highlights recent advances in imidazole-based drug discovery for cancer treatment.

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Area of Science:

  • Medicinal Chemistry
  • Organic Chemistry
  • Pharmacology

Background:

  • Nitrogen-containing heterocycles, particularly imidazole and fused imidazole rings, are prevalent in marketed drugs.
  • These structures possess unique properties like high polarity and hydrogen bonding capabilities, enabling interaction with biomolecules.
  • Imidazole derivatives exhibit a broad spectrum of biological activities, including significant anticancer potential.

Purpose of the Study:

  • To review recent advancements in imidazole and fused imidazole derivatives as anticancer agents.
  • To summarize findings from peer-reviewed literature published between 2018 and 2020.
  • To provide an overview of imidazole-based anticancer drug discovery and inspire future research.

Main Methods:

  • Literature review of peer-reviewed articles from 2018-2020.
  • Analysis of imidazole/fused imidazole derivatives reported to have anticancer activity.
  • Identification of targeted biomolecules and structure-activity relationships.

Main Results:

  • Imidazole/fused imidazole derivatives modulate various anticancer targets, including microtubules, kinases (tyrosine and serine-threonine), histone deacetylases, p53-Murine Double Minute 2 (MDM2) protein, poly (ADP-ribose) polymerase (PARP), and G-quadruplexes.
  • Compounds with anticancer activity via undefined mechanisms were also identified.
  • Key structure-activity relationships were described for these anticancer agents.

Conclusions:

  • Imidazole and fused imidazole scaffolds are versatile platforms for developing novel anticancer drugs.
  • Recent research demonstrates the potential of these compounds in targeting diverse cancer-related pathways.
  • Further exploration of imidazole derivatives holds promise for future anticancer drug discovery and development.