Marie Kirwen Erin, Batra Tarun, Karthikeyan Chandrabose, Deora Girdhar Singh, Rathore Vandana, Mulakayala Chaitanya, Mulakayala Naveen, Nusbaum Amy Catherine, Chen Joel, Amawi Haneen, McIntosh Kyle, Shivnath Neelam, Chowarsia Deepak, Sharma Nisha, Arshad Md, Trivedi Piyush, Tiwari Amit K
Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA.
School of Pharmaceutical Sciences, Rajiv Gandhi Technical University, Gandhi Nagar, Bhopal, MP 462036, India.
Acta Pharm Sin B. 2017 Jan;7(1):73-79. doi: 10.1016/j.apsb.2016.05.003. Epub 2016 Aug 6.
In this study we examined the suitability of the -imidazo[4,5-]pyridine ring system in developing novel anticancer and anti-inflammatory agents incorporating a diaryl pharmacophore. Eight 2,3-diaryl-3-imidazo[4,5-]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-3-imidazo[4,5-]pyridine derivatives were also evaluated for their COX-1 and COX-2 inhibitory activity . The results showed that compound exhibited 2-fold selectivity with IC values of 9.2 and 21.8 µmol/L against COX-2 and COX-1, respectively. Molecular docking studies on the most active compound revealed a binding mode similar to that of celecoxib in the active site of the COX-2 enzyme.
在本研究中，我们考察了-咪唑并[4,5-]吡啶环系统在开发含有二芳基药效团的新型抗癌和抗炎药物中的适用性。从我们的内部数据库中检索出的8种2,3-二芳基-3-咪唑并[4,5-]吡啶衍生物，针对9种癌细胞系评估了它们的细胞毒性活性。结果表明，这些化合物对MCF-7、MDA-MB-468、K562和SaOS2细胞表现出中等程度的细胞毒性活性，其中K562是这四种癌细胞系中最敏感的。还评估了这8种2,3-二芳基-3-咪唑并[4,5-]吡啶衍生物的COX-1和COX-2抑制活性。结果显示，化合物对COX-2和COX-1的IC值分别为9.2和21.8 µmol/L，表现出2倍的选择性。对活性最高的化合物进行的分子对接研究揭示了其在COX-2酶活性位点的结合模式与塞来昔布相似。
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