Design, Synthesis and Biological Evaluation of 2-（2-Aryl- morpholino-4-yl）ethyl Esters of Indomethacin as Potential Cyclooxygenase-2 （COX-2） Inhibitors

A number of novel 2-（2-arylmorpholino-4-yl）ethyl 1-（4-chlorobenzoyl）-5-methoxy-2-methyl-lH-indol-3- acetate hydrochlorides were synthesized and tested for their cyclooxygenase （COX-1 and COX-2） inhibition prop- erties in vitro. Many of these compounds exhibited moderate to good selective COX-2 inhibition, and subtle struc- tural changes in the substituents on the side chain of the ester moiety altered the inhibitory properties significantly. 2-[2-（4-Butoxyphenyl）morpholino-4-yl]ethyl 1-（4-chlorobenzoyl）-5-methoxy-2-methyl-IH-indol-3-acetate hydro- chloride （If）, showed good selective COX-2 inhibitory activity （Selective index （SI） 182）, which is comparative with celecoxib （SI 214）, a COX-2 inhibitor of diarylpyrazoles. While 2-[2-（2,4-dichloro-5-fluorophenyl）mor- pholino-4-yl]ethyl 1-（4-chlorobenzoyl）-5-methoxy-2-methyl-IH-indol-3-acetate hydrochloride （lg）, showed greater selective COX-2 inhibitory activity （SI 358） than celecoxib. Both compounds were identified as compromising de- rivatives in this class to reduce the side effects generated by nonsteroidal anti-inflammatory drugs （NSAIDs） indo- methacin.

MMPs与乳腺癌侵袭转移研究的现状

目的:探讨基质金属蛋白酶(MMPs)在肿瘤侵袭和转移过程中的作用机制及其在乳腺癌临床诊断与治疗中的应用价值。方法:以乳腺癌、侵袭转移和MMPs为关键词,检索近几年PubMed全文。纳入标准:1)肿瘤转移机制的最新研究进展;2)MMPs结构及生物学特性的研究;3)与乳腺癌相关的MMPs的最新研究进展。根据纳入标准,最后纳入分析28篇文献。结果:MMPs不仅降解细胞外基质,还促进或抑制肿瘤血管的新生,以及诱导肿瘤细胞免疫耐受。MMPs在乳腺癌中的特异性高表达,为乳腺癌的早期诊断与治疗提供了一种新思路。结论:MMPs与乳腺癌侵袭转移关系尤为密切,将有望成为乳腺癌临床研究中重要的诊断及判断预后的指标。