TY - JOUR
T1 - 2,3-Diaryl-3H-imidazo[4,5-b]pyridine derivatives as potential anticancer and anti-inflammatory agents
AU - Marie Kirwen, Erin
AU - Batra, Tarun
AU - Karthikeyan, Chandrabose
AU - Deora, Girdhar Singh
AU - Rathore, Vandana
AU - Mulakayala, Chaitanya
AU - Mulakayala, Naveen
AU - Nusbaum, Amy Catherine
AU - Chen, Joel
AU - Amawi, Haneen
AU - McIntosh, Kyle
AU - Sahabjada, null
AU - Shivnath, Neelam
AU - Chowarsia, Deepak
AU - Sharma, Nisha
AU - Arshad, Md
AU - Trivedi, Piyush
AU - Tiwari, Amit K.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - In this study we examined the suitability of the 3H-imidazo[4,5-b]pyridine ring system in developing novel anticancer and anti-inflammatory agents incorporating a diaryl pharmacophore. Eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives retrieved from our in-house database were evaluated for their cytotoxic activity against nine cancer cell lines. The results indicated that the compounds showed moderate cytotoxic activity against MCF-7, MDA-MB-468, K562 and SaOS2 cells, with K562 being the most sensitive among the four cancer cell lines. The eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives were also evaluated for their COX-1 and COX-2 inhibitory activity in vitro. The results showed that compound 3f exhibited 2-fold selectivity with IC50 values of 9.2 and 21.8 µmol/L against COX-2 and COX-1, respectively. Molecular docking studies on the most active compound 3f revealed a binding mode similar to that of celecoxib in the active site of the COX-2 enzyme.
AB - In this study we examined the suitability of the 3H-imidazo[4,5-b]pyridine ring system in developing novel anticancer and anti-inflammatory agents incorporating a diaryl pharmacophore. Eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives retrieved from our in-house database were evaluated for their cytotoxic activity against nine cancer cell lines. The results indicated that the compounds showed moderate cytotoxic activity against MCF-7, MDA-MB-468, K562 and SaOS2 cells, with K562 being the most sensitive among the four cancer cell lines. The eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives were also evaluated for their COX-1 and COX-2 inhibitory activity in vitro. The results showed that compound 3f exhibited 2-fold selectivity with IC50 values of 9.2 and 21.8 µmol/L against COX-2 and COX-1, respectively. Molecular docking studies on the most active compound 3f revealed a binding mode similar to that of celecoxib in the active site of the COX-2 enzyme.
KW - 3H-Imidazo[4,5-b]pyri-dine
KW - COX inhibitors
KW - Cytotoxicity
KW - Docking studies
KW - MTT assay
UR - http://www.scopus.com/inward/record.url?scp=84995646144&partnerID=8YFLogxK
U2 - 10.1016/j.apsb.2016.05.003
DO - 10.1016/j.apsb.2016.05.003
M3 - Article
AN - SCOPUS:84995646144
SN - 2211-3835
VL - 7
SP - 73
EP - 79
JO - Acta Pharmaceutica Sinica B
JF - Acta Pharmaceutica Sinica B
IS - 1
ER -
