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Li, J. et al.

One novel quinoxaline derivative as a potent human cyclophilin A inhibitor shows highly inhibitory activity against mouse spleen cell proliferation.

Cyclophilin A ( CypA) is a ubiquitous cellular enzyme playing critical roles in many biological processes, and its inhibitor has been reported to have potential immunosuppressive activity. In this work, we reported a novel quinoxaline derivative, 2,3-di(furan-2-yl)-6-(3-N,N-diethylcarbamoyl-piperidino)carbonylamino quinoxaline (DC838, 3), which was confirmed to be a potent inhibitor against human CypA. By using the surface plasmon resonance (SPR) and fluorescence titration techniques, the kinetic analysis of CypA/DC838 interaction was quantitatively performed. CypA peptidyl prolyl cis-trans isomerase ( PPIase) activity inhibition assay showed that DC838 demonstrated highly CypA PPIase inhibitory activity. In vivo assay results showed that DC838 could inhibit mouse spleen cell proliferation induced by concanavalin A ( Con A). Molecular docking simulation further elucidated the specific DC838 binding to CypA at the atomic level. The current work should provide useful information in the discovery of immunosuppressor based on CypA inhibitor.[1]

References

One novel quinoxaline derivative as a potent human cyclophilin A inhibitor shows highly inhibitory activity against mouse spleen cell proliferation. Li, J., Chen, J., Zhang, L., Wang, F., Gui, C., Zhang, L., Qin, Y., Xu, Q., Liu, H., Nan, F., Shen, J., Bai, D., Chen, K., Shen, X., Jiang, H. Bioorg. Med. Chem. (2006) [Pubmed]

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