Synthesis and Antiproliferative Activities of Benzimidazole-Based Sulfide and Sulfoxide Derivatives.

Journal: Scientia pharmaceutica
Published Date:

Abstract

The design, synthesis, and in vitro antiproliferative activity of a novel series of sulfide (4a-i) and sulfoxide (5a-h) derivatives of benzimidazole, in which different aromatic and heteroaromatic acetamides are linked to benzimidazole via sulfide (4a-i) and sulfoxide (5a-h) linker, are reported and the structure-activity relationship is discussed. The new derivatives were prepared by coupling 2-(mercaptomethyl)benzimidazole with 2-bromo-N-(substituted) acetamides in dry acetone in the presence of anhydrous potassium carbonate. With very few exceptions, all of the synthesized compounds showed varying antiprolific activities against HepG2, MCF-7, and A549 cell lines. Compound 5a was very similar in potency to doxorubicin as an anticancer drug, with IC50 values 4.1 ± 0.5, 4.1 ± 0.5, and 5.0 ± 0.6 µg/mL versus 4.2 ± 0.5, 4.9 ± 0.6, and 6.1 ± 0.6 µg/mL against HepG2, MCF-7, and A549 cell lines, respectively. In contrast, none of the compounds showed activity against human prostate PC3 cancer cells. Additionally, the sulfoxide derivatives were more potent than the corresponding sulfides.

Authors

  • Samir T Gaballah
    Photochemistry Department, Division of Chemical Industries, National Research Centre, El Buhoth St., Dokki 12622, Giza, Egypt.
  • Ahmed O H El-Nezhawy
    Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Saudi Arabia; Department of Chemistry of Natural and Microbial Products, National Research Centre, El Buhoth St., Dokki 12622, Giza, Egypt.
  • Hassan Amer
    Department of Chemistry of Natural and Microbial Products, National Research Centre, El Buhoth St., Dokki 12622, Giza, Egypt; Department of Chemistry, University of Natural Resources and Life Sciences, UFT Campus Tulln, Konrad-Lorenz-Straße 24, A-3430 Tulln, Austria.
  • Mamdouh Moawad Ali
    Biochemistry Department, Division of Genetic Engineering and Biotechnology, National Research Centre, El Buhoth St., Dokki 12622, Giza, Egypt.
  • Abeer Essam El-Din Mahmoud
    Biochemistry Department, Division of Genetic Engineering and Biotechnology, National Research Centre, El Buhoth St., Dokki 12622, Giza, Egypt.
  • Andreas Hofinger-Horvath
    Department of Chemistry, University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria.

Keywords

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