Synthesis, molecular modeling and bioevaluation of new benzimidazole derivatives as dual KSP (Kinesin Spindle Protein) and Aurora A Kinase inhibitors for antitumor activity

Authors

  • Asmaa A. Magd El-Din Department of Natural and Microbial Product, Research Division of Pharmaceutical and Drug Industries, National Research Centre, Giza, Egypt
  • Weam. S. El-serwy Department of Natural and Microbial Product, Research Division of Pharmaceutical and Drug Industries, National Research Centre, Giza, Egypt
  • Amira S. Abd El-All Department of Natural and Microbial Product, Research Division of Pharmaceutical and Drug Industries, National Research Centre, Giza, Egypt
  • N.M.A .El-Ebrashi Department of Natural and Microbial Product, Research Division of Pharmaceutical and Drug Industries, National Research Centre, Giza, Egypt
  • Mohamed M. Abdalla Research Unit, Saco Pharm. Co. 6 October city 11632, Egypt
  • Ahmed A. El-Rashedy Department of Natural and Microbial Product, Research Division of Pharmaceutical and Drug Industries, National Research Centre, Giza, Egypt

Abstract

A series of  dioxopyrimido[2,1-b][1,3]thiazine derivatives (3a-f,6a-e ) has been synthesized and their biological activities were also evaluated as potential dual KSP and Aurora A Kinase  inhibitors. Bioassay tests demonstrated that most of the compounds exhibited substantial broad-spectrum antitumor activity against the seven cancer cell lines (HepG2, SNB19, HT29, K562, A549-ATCC, MDA-MB-435 and SKOV3). Moreover, all the title compounds were assayed for as dual KSP and Aurora A kinase inhibition using the MT-activated ATPase assay. Compound (6b) displayed the most potent anticancer activities, which was comparable to the positive control and Molecular modeling has been done for this compound. The results may be used for developing a new class of inhibitors having a dual roles, KSP inhibition and Aurora-A kinase inhibition for the treatment of cancer.

Keywords:

Benzimidazole, Human cancer cells, Aurora A Kinase, KSP inhibition, Dioxopyrimido [2, 1-b] [1,3] Thiazine

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Published

05-04-2017
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How to Cite

Asmaa A. Magd El-Din, Weam. S. El-serwy, Amira S. Abd El-All, N.M.A .El-Ebrashi, Mohamed M. Abdalla, and Ahmed A. El-Rashedy. “Synthesis, Molecular Modeling and Bioevaluation of New Benzimidazole Derivatives As Dual KSP (Kinesin Spindle Protein) and Aurora A Kinase Inhibitors for Antitumor Activity”. Journal of Innovations in Pharmaceutical and Biological Sciences, vol. 4, no. 2, Apr. 2017, pp. 17-27, https://jipbs.com/index.php/journal/article/view/220.

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Research Article