Antineoplastic agents. 595. Structural modifications of betulin and the X-ray crystal structure of an unusual betulin amine dimer.
The lupane-type triterpene betulin (1) has been subjected to a series of structural modifications for the purpose of evaluating resultant cancer cell growth inhibitory activity. The reaction sequence 7→11→12 was especially noteworthy in providing a betulin-derived amine dimer. Other unexpected synthetic results included the 11 and 13/14→17 conversions, which yielded an imidazo derivative. X-ray crystal structures of dimer 12 and intermediate 25 are reported. All of the betulin modifications were examined for anticancer activity against the P388 murine and human cell lines. Significant cancer cell growth inhibition was found for 4, 8, 9, 15/16, 19, 20, 24, and 26, which further defines the utility of the betulin scaffold.
Department of Chemistry and Biochemistry, Arizona State University , P.O. Box 871604, Tempe, Arizona 85287-1604, United States.
George R
GR
Pettit
Noeleen
N
Melody
Frank
F
Hempenstall
Jean-Charles
JC
Chapuis
Thomas L
TL
Groy
Lee
L
Williams
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D029662:Betula / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007941:Leukemia P388; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D053978:Pentacyclic Triterpenes; D000094062:Betulinic Acid
D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; C480546:lupane; D053978:Pentacyclic Triterpenes; C002503:betulin; D000094062:Betulinic Acid