Cell-based biological evaluation of a new bisamide FMS kinase inhibitor possessing pyrrolo[3,2-c]pyridine scaffold

Mohammed I El-Gamal; Mohammed S Abdel-Maksoud; Mahmoud M Gamal El-Din; Kyung Ho Yoo; Daejin Baek; Chang-Hyun Oh

doi:10.1002/ardp.201400051

Cell-based biological evaluation of a new bisamide FMS kinase inhibitor possessing pyrrolo[3,2-c]pyridine scaffold

Arch Pharm (Weinheim). 2014 Sep;347(9):635-41. doi: 10.1002/ardp.201400051. Epub 2014 Jun 18.

Authors

Mohammed I El-Gamal¹, Mohammed S Abdel-Maksoud, Mahmoud M Gamal El-Din, Kyung Ho Yoo, Daejin Baek, Chang-Hyun Oh

Affiliation

¹ 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.

PMID: 24942978
DOI: 10.1002/ardp.201400051

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.

Keywords: Anticancer; Bisamide; Diarylamide; FMS kinase; Pyrrolo[3,2-c]pyridine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amides / chemical synthesis*
Amides / chemistry
Amides / pharmacology
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Fibroblasts / drug effects
Humans
Inhibitory Concentration 50
Macrophages, Peritoneal / drug effects
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacokinetics
Pyridines / chemistry*
Pyrroles / chemistry*
Receptor, Macrophage Colony-Stimulating Factor / antagonists & inhibitors*

Substances

Amides
Antineoplastic Agents
Protein Kinase Inhibitors
Pyridines
Pyrroles
pyrrolo(3,2-c)pyridine
Receptor, Macrophage Colony-Stimulating Factor