Regio-selective PEGylation of 14-deoxy-11, 12-didehydroandrographolide and their biological evaluation. Issue 39 (29th September 2016)

• Record Type: Journal Article
• Authors: Wang, Zhen; He, Ru; Chen, Yi; Wu, Feipeng
• Is Part Of: Tetrahedron. Volume 72:Issue 39(2016)
• Page Start: 5909
• Page End: 5913
• Publication Date: 2016-09-29
• Subjects: 14-Deoxy-11, 12-didehydroandrographolides -- Region-selective PEGylation -- Solubility -- Bioactivity -- Synthesis; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2016.08.024
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: Poor water solubility limits the clinical use of 14-deoxy-11, 12-didehydroandrographolide (DA ). To develop a simple and efficient approach to improving water solubility ofDA, polyethylene glycol methyl ether (mPEG350, average MW=350) as hydrophilic group is employed. Two PEGylatedDA derivativesDA-1 (mPEG350 at C19 -position) andDA-2 (mPEG350 at C3 -position) are synthesized and evaluated to inhibit the cell proliferation of HepG-2 cells in vitro. As expected, the aqueous solubility ofDA-1 andDA-2 is significantly improved (ca. 200 mg/mL, 25 °C), and both exhibit good partition coefficient (log P≥1.6). It is found thatDA-1 shows tumor-inhibition activity and more than 60% cell inhibition is obtained. Graphical abstract: