2,3-Diaryl-3H-imidazo[4,5-b]pyridine derivatives as potential anticancer and anti-inflammatory agents

Erin Marie Kirwen; Tarun Batra; Chandrabose Karthikeyan; Girdhar Singh Deora; Vandana Rathore; Chaitanya Mulakayala; Naveen Mulakayala; Amy Catherine Nusbaum; Joel Chen; Haneen Amawi; Kyle McIntosh; Sahabjada; Neelam Shivnath; Deepak Chowarsia; Nisha Sharma; Md Arshad; Piyush Trivedi; Amit K. Tiwari

doi:10.1016/j.apsb.2016.05.003

2,3-Diaryl-3H-imidazo[4,5-b]pyridine derivatives as potential anticancer and anti-inflammatory agents

Erin Marie Kirwen
, Tarun Batra
, Chandrabose Karthikeyan
, Girdhar Singh Deora
, Vandana Rathore
, Chaitanya Mulakayala
, Naveen Mulakayala
, Amy Catherine Nusbaum
, Joel Chen
, Haneen Amawi
, Kyle McIntosh
, Sahabjada
, Neelam Shivnath
, Deepak Chowarsia
, Nisha Sharma
, Md Arshad
, Piyush Trivedi
, Amit K. Tiwari

University of Toledo
Rajiv Gandhi Technical University
University of Queensland
University of Hyderabad
Sri Sathya Sai University
Clearsynth Labs Ltd
University of Lucknow
Chhatrapati Shahu Ji Maharaj Kanpur University

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	73-79
Number of pages	7
Journal	Acta Pharmaceutica Sinica B
Volume	7
Issue number	1
DOIs	https://doi.org/10.1016/j.apsb.2016.05.003
State	Published - 1 Jan 2017
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

3H-Imidazo[4,5-b]pyri-dine
COX inhibitors
Cytotoxicity
Docking studies
MTT assay

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10.1016/j.apsb.2016.05.003

Cite this

Marie Kirwen, E., Batra, T., Karthikeyan, C., Deora, G. S., Rathore, V., Mulakayala, C., Mulakayala, N., Nusbaum, A. C., Chen, J., Amawi, H., McIntosh, K., Sahabjada, Shivnath, N., Chowarsia, D., Sharma, N., Arshad, M., Trivedi, P., & Tiwari, A. K. (2017). 2,3-Diaryl-3H-imidazo[4,5-b]pyridine derivatives as potential anticancer and anti-inflammatory agents. Acta Pharmaceutica Sinica B, 7(1), 73-79. https://doi.org/10.1016/j.apsb.2016.05.003

@article{8cd43ac939e14f98a4c741f5f669fcfc,

title = "2,3-Diaryl-3H-imidazo[4,5-b]pyridine derivatives as potential anticancer and anti-inflammatory agents",

abstract = "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.",

keywords = "3H-Imidazo[4,5-b]pyri-dine, COX inhibitors, Cytotoxicity, Docking studies, MTT assay",

author = "\{Marie Kirwen\}, Erin and Tarun Batra and Chandrabose Karthikeyan and Deora, \{Girdhar Singh\} and Vandana Rathore and Chaitanya Mulakayala and Naveen Mulakayala and Nusbaum, \{Amy Catherine\} and Joel Chen and Haneen Amawi and Kyle McIntosh and Sahabjada and Neelam Shivnath and Deepak Chowarsia and Nisha Sharma and Md Arshad and Piyush Trivedi and Tiwari, \{Amit K.\}",

note = "Publisher Copyright: {\textcopyright} 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences",

year = "2017",

month = jan,

day = "1",

doi = "10.1016/j.apsb.2016.05.003",

language = "English",

volume = "7",

pages = "73--79",

journal = "Acta Pharmaceutica Sinica B",

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publisher = "Chinese Academy of Medical Sciences",

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Marie Kirwen, E, Batra, T, Karthikeyan, C, Deora, GS, Rathore, V, Mulakayala, C, Mulakayala, N, Nusbaum, AC, Chen, J, Amawi, H, McIntosh, K, Sahabjada, Shivnath, N, Chowarsia, D, Sharma, N, Arshad, M, Trivedi, P & Tiwari, AK 2017, '2,3-Diaryl-3H-imidazo[4,5-b]pyridine derivatives as potential anticancer and anti-inflammatory agents', Acta Pharmaceutica Sinica B, vol. 7, no. 1, pp. 73-79. https://doi.org/10.1016/j.apsb.2016.05.003

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,

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 - https://www.scopus.com/pages/publications/84995646144

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 -

2,3-Diaryl-3H-imidazo[4,5-b]pyridine derivatives as potential anticancer and anti-inflammatory agents

Abstract

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Keywords

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