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Related Concept Videos

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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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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.
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Thiazepine-Based Hybrids as Promising Anti-Colon Cancer Agents: Design, Synthesis, Computational and In Vitro

Mahesh D Vaghasiya1, Arindam Sain2, Jigarkumar V Mendapara1

  • 1Department of Chemistry, S.V. National Institute of Technology, Surat, Gujarat, 395007, India.

Chemistry & Biodiversity
|October 16, 2024
PubMed
Summary

Novel thiazepine hybrids show potent anti-colon cancer activity. Compounds 9b, 9c, and 9d demonstrate significant cytotoxicity against HT-29 cells, paving the way for new colon cancer therapeutics.

Keywords:
Colorectal cancerComputational analysisEGFRHT-29 cellsThiazepine hybrids

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Area of Science:

  • Medicinal Chemistry
  • Oncology
  • Pharmacology

Background:

  • Colon cancer remains a significant global health challenge.
  • Developing novel therapeutic agents with high efficacy and safety is crucial.

Purpose of the Study:

  • To design and synthesize novel thiazepine-based hybrids as potential lead molecules for anti-colon cancer therapy.
  • To evaluate the in vitro cytotoxic effects of these compounds against colon cancer cells.
  • To computationally assess pharmacokinetic and safety profiles (ADMET).

Main Methods:

  • Synthesis of thiazepine-based hybrids (compounds 9a-d).
  • Characterization using IR, NMR, and HR-MS analytical techniques.
  • In vitro cytotoxicity assays on HT-29 colon cancer cells at 24h and 48h.
  • In silico ADMET prediction for pharmacokinetic and safety profiling.

Main Results:

  • All synthesized compounds exhibited dose-dependent cytotoxicity against HT-29 cells.
  • Compounds 9b, 9c, and 9d showed significant efficacy, with 9d being particularly potent at 48h exposure (50% cell death at ~5 μM).
  • Compound 9a displayed lower cytotoxicity compared to the other tested hybrids.
  • In silico studies provided insights into potential drug targets and safety profiles.

Conclusions:

  • Thiazepine-based hybrids represent promising candidates for colon cancer treatment.
  • Compounds 9b, 9c, and 9d warrant further investigation as lead anti-colon cancer agents.
  • The study highlights the potential of these novel compounds in exploring mechanistic actions against colon cancer.