Syntheses and biological evaluation of vinblastine congeners.
Sixty-two congeners of vinblastine (VLB), primarily with modifications of the piperidine ring in the carbomethoxycleavamine moiety of the binary alkaloid, were synthesized and evaluated for cytotoxicity against murine L1210 leukemia and RCC-2 rat colon cancer cells, and for their ability to inhibit polymerization of microtubular protein at < 10(-6) M, and for induction of spiralization of microtubular protein, and for microtubular disassembly at 10(-4) M concentrations. An ID50 range of >10(7) M concentrations was found for L1210 inhibition by these compounds, with the most active 1000x as potent as vinblastine.
Kuehne
Martin E
ME
Department of Chemistry, University of Vermont, Burlington, VT 05405, USA.
Bornmann
William G
WG
Markó
Istvan
I
Qin
Yong
Y
LeBoulluec
Karen L
KL
Frasier
Deborah A
DA
Xu
Feng
F
Mulamba
Tshilundu
T
Ensinger
Carol L
CL
Borman
Linda S
LS
Huot
Anne E
AE
Exon
Christopher
C
Bizzarro
Fred T
FT
Cheung
Julia B
JB
Bane
Susan L
SL
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy; D004354:Drug Screening Assays, Antitumor; D020128:Inhibitory Concentration 50; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008870:Microtubules / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine