Korean Medical School, Kyung Hee University, Hoegi-dong, Dongdaemoon-ku, Seoul 130-701, Republic of Korea.
Center for Biomaterials, Korea Institute of Science and Technology (KIST), PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea; Department of Biomolecular Science, University of Science and Technology (UST), 113 Gwahangno, Yuseong-gu, Daejeon 305-333, Republic of Korea; Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
Bioorg Med Chem Lett. 2014 Jan 15;24(2):571-5. doi: 10.1016/j.bmcl.2013.12.018. Epub 2013 Dec 10.
The regulations of NO and PGE2 productions are research topics of interest in the field of antiinflammatory drug development. In the present study, a series of tricyclic fused coumarin sulfonate derivatives was synthesized and evaluated for their abilities to inhibit NO and PGE2 productions in LPS-induced RAW 264.7 macrophages. Among all the target compounds, compound 1g possessing p-(trifluoromethyl)phenyl and fused cycloheptane moieties showed the highest inhibitory effects on NO and PGE2 productions. Compound 1g not only inhibited COX-2 activity but also reduced expressions of COX-2 and iNOS. Furthermore, ADME profiling showed that compounds 1g, 1j, 1m, and 1n are estimated to be orally bioavailable.
NO 和 PGE2 产生的调节是抗炎药物开发领域的研究课题。在本研究中，合成了一系列三环稠合香豆素磺酸盐衍生物，并评估了它们抑制 LPS 诱导的 RAW 264.7 巨噬细胞中 NO 和 PGE2 产生的能力。在所合成的目标化合物中，具有 p-(三氟甲基)苯基和稠合环己烷部分的化合物 1g 对 NO 和 PGE2 的产生表现出最高的抑制作用。化合物 1g 不仅抑制 COX-2 活性，还降低 COX-2 和 iNOS 的表达。此外，ADME 分析表明，化合物 1g、1j、1m 和 1n 预计具有口服生物利用度。
