Part II: New candidates of pyrazole-benzimidazole conjugates as checkpoint kinase 2 (Chk2) inhibitors.
Autor: | Galal SA; Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Cairo, 12622, Egypt. Electronic address: sh12galal@hotmail.com., Khairat SHM; Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Cairo, 12622, Egypt., Ali HI; Department of Pharmaceutical Sciences, Texas A&M University Irma Lerma Rangel College of Pharmacy Kingsville, TX 78363, United States; Department of Pharmaceutical Chemistry, College of Pharmacy, Helwan University, Cairo, Egypt., Shouman SA; Department of Cancer Biology, National Cancer Institute, Cairo University, Egypt., Attia YM; Department of Cancer Biology, National Cancer Institute, Cairo University, Egypt., Ali MM; Department of Biochemistry, Division of Genetic Engineering and Biotechnology, National Research Centre, 12622, Cairo, Egypt., Mahmoud AE; Department of Biochemistry, Division of Genetic Engineering and Biotechnology, National Research Centre, 12622, Cairo, Egypt., Abdel-Halim AH; Department of Biochemistry, Division of Genetic Engineering and Biotechnology, National Research Centre, 12622, Cairo, Egypt., Fyiad AA; Department of Biochemistry, Division of Genetic Engineering and Biotechnology, National Research Centre, 12622, Cairo, Egypt., Tabll A; Department of Microbial Biotechnology, Division of Genetic Engineering & Biotechnology, National Research Centre, 12622, Cairo, Egypt., El-Shenawy R; Department of Microbial Biotechnology, Division of Genetic Engineering & Biotechnology, National Research Centre, 12622, Cairo, Egypt., El Abd YS; Department of Microbial Biotechnology, Division of Genetic Engineering & Biotechnology, National Research Centre, 12622, Cairo, Egypt., Ramdan R; Radiobiology Unit, Belgian Nuclear Research Center (SCK•CEN), Mol, Belgium; Department of Basic Medical Sciences, Physiology Group, Ghent University, Ghent, Belgium., El Diwani HI; Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Cairo, 12622, Egypt. |
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Jazyk: | angličtina |
Zdroj: | European journal of medicinal chemistry [Eur J Med Chem] 2018 Jan 20; Vol. 144, pp. 859-873. Date of Electronic Publication: 2017 Dec 08. |
DOI: | 10.1016/j.ejmech.2017.12.023 |
Abstrakt: | The development of checkpoint kinase 2 (Chk2) inhibitors for the treatment of cancer has been an ongoing and attractive objective in drug discovery. In this study, twenty-one feasible pyrazole-benzimidazole conjugates were synthesized to study their effect against Chk2 activity using Checkpoint Kinase Assay. The antitumor activity of these compounds was investigated using SRB assay. A potentiation effect of the synthesized Chk2 inhibitors was also investigated using the genotoxic anticancer drugs cisplatin and doxorubicin on breast carcinoma, (ER+) cell line (MCF-7). In vivo Chk2 and antitumor activities of 8d as a single-agent, and in combination with doxorubicin, were evaluated in breast cancer bearing animals induced by N-methylnitrosourea. The effect of 8d alone and in combination with doxorubicin was also studied on cell-cycle phases of MCF-7 cells using flow cytometry analysis. The results revealed their potencies as Chk2 inhibitors with IC (Copyright © 2017 Elsevier Masson SAS. All rights reserved.) |
Databáze: | MEDLINE |
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