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Cell‐Based Biological Evaluation of a New Bisamide FMS Kinase Inhibitor Possessing Pyrrolo[3,2‐ c ]pyridine Scaffold
Author(s) -
ElGamal Mohammed I.,
AbdelMaksoud Mohammed S.,
ElDin Mahmoud M. Gamal,
Yoo Kyung Ho,
Baek Daejin,
Oh ChangHyun
Publication year - 2014
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201400051
Subject(s) - kinase , chemistry , selectivity , pyridine , cell culture , ic50 , potency , cell growth , lead compound , stereochemistry , growth inhibition , biological activity , structure–activity relationship , biochemistry , biology , in vitro , medicinal chemistry , genetics , catalysis
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 IC 50 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.