Deoxyartemisinin derivatives from photooxygenation of anhydrodeoxydihydroartemisinin and their cytotoxic evaluation.
Photooxygenation of anhydrodeoxydihydroartemisinin (4) followed by chromatographic separation of the reaction mixture yielded the new compounds alpha- (5) and beta-hydroperoxydeoxyartemisitene (8) and the formate ester 7, together with two previously reported compounds, 6 and 9. Reduction of 5 using polymer-bound triphenylphosphine afforded the new compound dihydrodeoxyartemisitene (10). Treatment of 10 with a catalytic amount of BF(3)-OEt(2) yielded the C(2)-symmetrical dimer bis(dihydrodeoxyartemisitene) ether (11) and two new compounds, dihydrodeoxyartemisitene methyl ether (12) and the dimer 13, as minor products. Dehydroacetoxylation of 5 using acetic anhydride in pyridine afforded deoxyartemisitene (14). The identities of the new compounds (5, 7, 8, 10-14) were deduced from their spectral data and by chemical derivatization. The stereochemistry of dimer 11 was defined on the basis of X-ray crystallographic analysis. All compounds were evaluated in vitro in the National Cancer Institute drug-screening program consisting of 60 human cancer cell lines derived from nine different tissues. Of the compounds tested, deoxyartemisitene (14) demonstrated significant cytotoxicity against a number of human cancer cell lines.
Galal
Ahmed M
AM
National Center for Natural Products Research, University of Mississippi, 38677, USA. amgalalv@yahoo.com
Ross
Samir A
SA
ElSohly
Mahmoud A
MA
ElSohly
Hala N
HN
El-Feraly
Farouk S
FS
Ahmed
Mohamed S
MS
McPhail
Andrew T
AT
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019306:Artemisia / Q000737:chemistry*; D037621:Artemisinins; D001943:Breast Neoplasms; D002289:Carcinoma, Non-Small-Cell Lung; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D010777:Photochemistry; D012529:Saudi Arabia; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D037621:Artemisinins; D012717:Sesquiterpenes; C089918:anhydrodihydroartemisinin; C055261:deoxyartemisinin; C031327:artemisinin; D010100:Oxygen