360788-05-2Relevant academic research and scientific papers
Syntheses and biological evaluation of vinblastine congeners.
Kuehne, Martin E,Bornmann, William G,Marko, Istvan,Qin, Yong,LeBoulluec, Karen L,Frasier, Deborah A,Xu, Feng,Mulamba, Tshilundu,Ensinger, Carol L,Borman, Linda S,Huot, Anne E,Exon, Christopher,Bizzarro, Fred T,Cheung, Julia B,Bane, Susan L
, p. 2120 - 2136 (2007/10/03)
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(7) M concentrations was found for L1210 inhibition by these compounds, with the most active 1000x as potent as vinblastine.
Syntheses of 5a′-homo-vinblastine and congeners designed to establish structural determinants for isolation of atropisomers
Kuehne,Cowen,Xu,Borman
, p. 5303 - 5316 (2007/10/03)
The syntheses of 5a′-homo-vinblastine (3a) and its C-20′ methyl congener 62a were achieved. In contrast to vinblastine, these compounds did not allow isolation of atropisomers because of their lower conformational inversion barrier. However, annelation of a six-membered ring to the conformationally mobile D′-piperidine ring provided an isolated atropisomer 81a, which could be converted to its lower energy conformation 65a on heating. The 5a′-homo-vinblastine congeners 3a, 62a, and 65a showed vinblastine-like inhibition of tubulin polymerization and cytotoxicity to L1210 leukemia cells, albeit at lower potency for the latter activity, than that found with the corresponding compounds in the vinblastine series.
