2-((Benzimidazol-2-yl)thio)-1-arylethan-1-ones: Synthesis, crystal study and cancer stem cells CD133 targeting potential

Abdel-Aziz HA 1 , Ghabbour HA 2 , Eldehna WM 3 , Al-Rashood ST 2 , Al-Rashood KA 2 , Fun HK 4 Show all authors , Al-Tahhan M 5 , Al-Dhfyan A 5

Affiliations 

  • 1 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia; Department of Applied Organic Chemistry, National Research Centre, Dokki, Giza, P.O. Box 12622, Egypt. Electronic address: [email protected]
  • 2 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia
  • 3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt
  • 4 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia; X-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800, USM, Penang, Malaysia
  • 5 Stem Cell & Tissue Re-Engineering Program, Research Center, King Faisal Specialized Hospital & Research Center, MBC-03, PO Box 3354, Riyadh, 11211, Saudi Arabia
Eur J Med Chem, 2015 Nov 2;104:1-10.
PMID: 26413725 DOI: 10.1016/j.ejmech.2015.09.023

Abstract

In order to develop a potent anti-tumor agent that can target both cancer stem cells and the bulk of tumor cells, a series of 2-((benzimidazol-2-yl)thio)-1-arylethan-1-ones 5a-o was synthesized. All compounds were evaluated for their anti-proliferative activity towards colon HT-29 cancer cell line. In addition, their inhibitory effect against cell surface expression of CD133, a potent cancer stem cells (CSCs) marker, in the same cells was evaluated by flow cytometry at 10 μM. Compound 5l emerged as the most active anti-proliferative analog against HT-29 (IC50 = 18.83 ± 1.37 μM), that almost equipotent as 5-fluorouracil (IC50 = 15.83 ± 1.63 μM) with 50.11 ± 4.05% inhibition effect on CD133 expression, suggested dual targeted effect. Also, compounds 5h, 5j, 5k and 5m-o inhibited the expression of CD133 with more than 50%. The SAR study pointed out the significance of substitution of the pendent phenyl group with lipophilic electron-donating groups or replacing it by 2-thienyl or 2-furyl groups.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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