title: Synthesis, Crystal Study, and Anti-Proliferative Activity of Some 2-Benzimidazolylthioacetophenones towards Triple-Negative Breast Cancer MDA-MB-468 Cells as Apoptosis-Inducing Agents.
abstract: On account of its poor prognosis and deficiency of therapeutic stratifications, triple negative breast cancer continues to form the causative platform of an incommensurate number of breast cancer deaths. Aiming at the development of potent anticancer agents as a continuum of our previous efforts, a novel series of 2-((benzimidazol-2-yl)thio)-1-arylethan-1-ones 5a-w was synthesized and evaluated for its anti-proliferative activity towards triple negative breast cancer (TNBC) MDA-MB-468 cells. Compound 5k was the most active analog against MDA-MB-468 (IC50 = 19.90 ± 1.37 µM), with 2.1-fold increased activity compared to 5-fluorouracil (IC50 = 41.26 ± 3.77 µM). Compound 5k was able to induce apoptosis in MDA-MB-468, as evidenced by the marked boosting in the percentage of florecsein isothiocyanate annexin V (Annexin V-FITC)-positive apoptotic cells (upper right (UR) + lower right (LR)) by 2.8-fold in comparison to control accompanied by significant increase in the proportion of cells at pre-G1 (the first gap phase) by 8.13-fold in the cell-cycle analysis. Moreover, a quantitative structure activity relationship (QSAR) model was established to investigate the structural requirements orchestrating the anti-proliferative activity. Finally, we established a theoretical kinetic study.
authors.affiliation: Department of Applied Organic Chemistry, National Research Center, Dokki, Giza 12622, Egypt. hatem_741@yahoo.com.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Abdel-Aziz
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. wagdy2000@gmail.com.
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. ghabbourh@yahoo.com.|Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. ghabbourh@yahoo.com.
authors.forename: Hazem
authors.initials: H
authors.lastname: Ghabbour
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo 11566, Egypt. ghada.mohamed@pharma.asu.edu.eg.
authors.forename: Ghada H
authors.initials: GH
authors.lastname: Al-Ansary
authors.affiliation: Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan. areej_assaf@ju.edu.jo.
authors.forename: Areej M
authors.initials: AM
authors.lastname: Assaf
authors.affiliation: Stem Cell &amp; Tissue Re-Engineering Program, Research Center, King Faisal Specialized Hospital &amp; Research Center, MBC-03, P.O. Box 3354, Riyadh 11211, Saudi Arabia. pharm101696@hotmail.com.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al-Dhfyan
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology*; D001681:Biological Assay; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003460:Crystallization; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles
keywords: X-ray; anti-proliferative; apoptosis; breast cancer MDA-MB-468 cells; synthesis