title: 2-((Benzimidazol-2-yl)thio)-1-arylethan-1-ones: Synthesis, crystal study and cancer stem cells CD133 targeting potential.
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.
authors.affiliation: 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: hatem_741@yahoo.com.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Abdel-Aziz
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
authors.forename: Hazem A
authors.initials: HA
authors.lastname: Ghabbour
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt.
authors.forename: Wagdy M
authors.initials: WM
authors.lastname: Eldehna
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
authors.forename: Sara T A
authors.initials: ST
authors.lastname: Al-Rashood
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
authors.forename: Khalid A
authors.initials: KA
authors.lastname: Al-Rashood
authors.affiliation: 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.
authors.forename: Hoong-Kun
authors.initials: HK
authors.lastname: Fun
authors.affiliation: Stem Cell & Tissue Re-Engineering Program, Research Center, King Faisal Specialized Hospital & Research Center, MBC-03, PO Box 3354, Riyadh, 11211, Saudi Arabia.
authors.forename: Mays
authors.initials: M
authors.lastname: Al-Tahhan
authors.affiliation: Stem Cell & Tissue Re-Engineering Program, Research Center, King Faisal Specialized Hospital & Research Center, MBC-03, PO Box 3354, Riyadh, 11211, Saudi Arabia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al-Dhfyan
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019073:HT29 Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides
keywords: Anti-proliferative; CD133 (prominin-1); Cancer stem cells; Synthesis; X-ray