title: New substituted C-19-andrographolide analogues with potent cytotoxic activities.
abstract: Andrographolide, the major diterpenoid lactone from Andrographis paniculata, is toxic against cancer cells. In the present study, we investigated the structure-activity relationships (SARs) of 19 andrographolide analogues which were synthesized by modification at the three hydroxyl groups. A number of the andrographolide analogues showed much higher cytotoxic activities than that of the parent compound on cancer cells including P-388, KB, COL-2, MCF-7, LU-1 and ASK cells. SAR studies of the synthetic analogues indicated that the introduction of silyl ether or triphenylmethyl ether group into C-19 of the parent compound led to increase in toxicity against the cancer cells. The 19-O-triphenylmethyl ether analogue 18 showed higher cytotoxic activity than the potent anticancer drug ellipticine, and this analogue may serve as a potential structure lead for the development of new anticancer drugs.
authors.affiliation: Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand.
authors.forename: Uthaiwan
authors.initials: U
authors.lastname: Sirion
authors.forename: Sakkasem
authors.initials: S
authors.lastname: Kasemsook
authors.forename: Kanoknetr
authors.initials: K
authors.lastname: Suksen
authors.forename: Pawinee
authors.initials: P
authors.lastname: Piyachaturawat
authors.forename: Apichart
authors.initials: A
authors.lastname: Suksamrarn
authors.forename: Rungnapha
authors.initials: R
authors.lastname: Saeeng
mesh_terms: D035685:Andrographis / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004224:Diterpenes / Q000737:chemistry*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000494:pharmacology; D008956:Models, Chemical; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D007783:Lactones; C030419:andrographolide