jm500530v_si_001.pdf (4.2 MB)
One-Pot Synthesis of Vinca Alkaloids–Phomopsin Hybrids
journal contribution
posted on 2014-06-26, 00:00 authored by Olga Gherbovet, Claire Coderch, María
Concepción García Alvarez, Jérôme Bignon, Sylviane Thoret, Françoise Guéritte, Federico Gago, Fanny RoussiHybrids
of vinca alkaloids and phomopsin A have been elaborated
with the aim of interfering with the “vinca site” and
the “peptide site” of the vinca domain in tubulin. They
were synthesized by an efficient one-pot procedure that directly links
the octahydrophomopsin lateral chain to the velbenamine moiety of
7′-homo-anhydrovinblastine. In their modeled
complexes with tubulin, these hybrids were found to superimpose nicely
on the tubulin-bound structures of vinblastine and phomopsin A. This
good matching can account for the fact that two of them are very potent
inhibitors of microtubules assembly and are cytotoxic against four
cancer cell lines.