title: New benzimidazoles and their antitumor effects with Aurora A kinase and KSP inhibitory activities.
abstract: A newly synthesized series of anticancer compounds comprising thiazolo[3,2-a]pyrimidine derivatives 6a-q bearing a benzimidazole moiety was produced via a one-pot reaction of N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-2-cyanoacetamide 5 with 2-aminothiazole and an appropriate aromatic aldehyde. Compound 7 was obtained via the reaction of 4-(1H-benzo[d]imidazol-2yl)benzenamide 1 with carbon disulphide and methyl iodide in the presence of concentrated aqueous solution of NaOH, then treated with o-phenylenediamine to give N-(4-1H-benzo[d]imidazol-2-yl)phenyl)-1H-benzo[d]imidazol-2-amine 8. The structures of the newly synthesized compounds were confirmed by analytical and spectroscopic measurements (IR, MS, and (1) H NMR). The synthesized products were screened and studied for their in vitro antitumor activity against three human cancer cell lines (namely colorectal cancer cell line HCT116, human liver cancer cell line HepG2, and human ovarian cancer cell line A2780) and their Aurora A kinase and KSP inhibitory activities. All newly synthesized compounds revealed marked results comparable with the standard drug CK0106023. The compounds 6e and 6k of the thiazolopyrimidine derivatives were the most active compounds when tested against the three cell lines in comparison with the standard drug CK0106023, and showed potent dual KSP and Aurora A kinase inhibition.
authors.affiliation: Department of Natural and Microbial Product, Research Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, Cairo, Egypt.
authors.forename: Amira S
authors.initials: AS
authors.lastname: Abd El-All
authors.affiliation: Department of Natural and Microbial Product, Research Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, Cairo, Egypt.
authors.forename: Asmaa A
authors.initials: AA
authors.lastname: Magd-El-Din
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Giza, Egypt.
authors.forename: Fatma A F
authors.initials: FA
authors.lastname: Ragab
authors.affiliation: Biomedical Informatics and Chemoinformatics Group, Center of Excellence for Advanced Sciences, National Research Centre, Dokki, Cairo, Egypt.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: ElHefnawi
authors.affiliation: Research Unit, Saco Pharm. Co., 6 October City, Egypt.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Abdalla
authors.affiliation: Department of Natural and Microbial Product, Research Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, Cairo, Egypt.
authors.forename: Shadia A
authors.initials: SA
authors.lastname: Galal
authors.affiliation: Department of Natural and Microbial Product, Research Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, Cairo, Egypt.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: El-Rashedy
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; C470243:KIF11 protein, human; C576917:AURKA protein, human; D064096:Aurora Kinase A; D016547:Kinesins
keywords: Aurora A kinase inhibition; Benzimidazole; Human cancer cells; KSP inhibition; Thiazolo[3,2-a]pyrimidine