title: Cell-based biological evaluation of a new bisamide FMS kinase inhibitor possessing pyrrolo[3,2-c]pyridine scaffold.
abstract: A bisamide compound 1 possessing the pyrrolo[3,2-c]pyridine nucleus was synthesized and biologically evaluated. It was tested for kinase inhibitory activity over a panel of 47 kinases, and its selectivity toward the FMS kinase was accidentally discovered. Compound 1 was tested over a panel of seven ovarian, two prostate, and six breast cancer cell lines at a single dose concentration of 10 µM and showed high activity. It was further tested in a 5-dose mode to determine its IC50 and total growth inhibition (TGI) values over the 15 cell lines. Compound 1 showed high potency on the submicromolar scale and good efficacy. The cytotoxic effect of compound 1 over peritoneal macrophages was also investigated. Compound 1 demonstrated higher selectivity against different cancer cell lines compared with HS-27 fibroblasts.
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology, Seoul, Republic of Korea; Faculty of Pharmacy, Department of Medicinal Chemistry, University of Mansoura, Mansoura, Egypt.
authors.forename: Mohammed I
authors.initials: MI
authors.lastname: El-Gamal
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Abdel-Maksoud
authors.forename: Mahmoud M Gamal
authors.initials: MM
authors.lastname: El-Din
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Yoo
authors.forename: Daejin
authors.initials: D
authors.lastname: Baek
authors.forename: Chang-Hyun
authors.initials: CH
authors.lastname: Oh
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D017737:Macrophages, Peritoneal / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011725:Pyridines / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011758:Pyrroles; C475261:pyrrolo(3,2-c)pyridine; D016186:Receptor, Macrophage Colony-Stimulating Factor
keywords: Anticancer; Bisamide; Diarylamide; FMS kinase; Pyrrolo[3,2-c]pyridine