New benzimidazole derivatives containing hydrazone group as anticancer agents: Inhibition of carbonic anhydrase IX and molecular docking studies.

in Archiv der Pharmazie by Hayrani Eren Bostancı, Mehmet Taha Yıldız, Serkan Kapancık, Zeynep Deniz Şahin Inan, Hacı Ahmet Kılıç, Özen Özensoy Güler, Ulviye Acar Çevik, Yusuf Özkay, Zafer Asım Kaplancıklı

TLDR

  • Novel benzimidazole-hydrazone derivatives 3d and 3j demonstrate potent anti-cancer activity against breast cancer, glioma, and colon cancer cells, and may be effective as CA IX inhibitors.
  • Compound 3d shows promise as a potential anti-cancer agent with a more significant effect than cisplatin.
  • Further research is needed to fully explore the potential of these compounds and to understand their mechanisms of action.

Abstract

In this study, we propose identifying potential novel compounds targeting carbonic anhydrase (CA) IX and anticancer activity. To study the impact of these synthesized compounds on CA IX and anticancer activity, we have developed and synthesized novel benzimidazole-hydrazone derivatives (3a-3j). The target compounds'H NMR (nuclear magnetic resonance),C NMR, and high resolution mass spectrometry spectra were used to confirm their chemical structures. L929 (healthy mouse fibroblast cell line) used as control healthy cell line and MCF-7 (breast cancer), C6 (rat glioblastoma), HT-29 (colon cancer), cells were used in cell culture studies. As a result of cell culture studies, it was determined that the newly synthesized compounds 3d and 3j had cytotoxic effects on colon cancer. Again, it was determined that the compound 3d had a more toxic effect than cisplatin on both breast cancer and glioma cells. According to the CA IX activity results, compounds 3d and 3j were found to have the highest activity. Compounds 3d and 3j are essential for having anti-cancer properties and inhibiting the carbonic anhydrase IX enzyme. Molecular docking of these compounds was carried out in the active site of CA IX. Flow cytometry and immunofluorescence microscope analyses also confirmed that these compounds had cytotoxic effects on cancer cells.

Overview

  • This study aims to identify novel compounds targeting carbonic anhydrase (CA) IX and anticancer activity using benzimidazole-hydrazone derivatives.
  • The study includes the synthesis and characterization of 9 novel compounds, and their effects on healthy and cancerous cell lines are explored.
  • The primary objective of the study is to investigate the potential of these compounds as anti-cancer agents and CA IX inhibitors.

Comparative Analysis & Findings

  • Compound 3d was found to have the most potent cytotoxic effect on breast cancer and glioma cells, with a more significant effect than cisplatin.
  • Compounds 3d and 3j were found to have the highest activity against CA IX, making them essential candidates for further study as anti-cancer agents.
  • Cell culture studies and molecular docking experiments confirmed the cytotoxic effects of compounds 3d and 3j on cancer cells, and flow cytometry and immunofluorescence microscopy analyses further supported these findings.

Implications and Future Directions

  • The study's findings suggest that compounds 3d and 3j may be effective as anti-cancer agents, particularly against breast cancer and glioma.
  • Further studies are needed to fully explore the potential of these compounds and to understand their mechanisms of action.
  • The development of novel CA IX inhibitors and anti-cancer agents with improved efficacy and reduced toxicity may lead to improved treatment options for cancer patients.
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