2008/12/12 by Quoc Anh Ngo, Fanny Roussi, Anthony Cormier +4 · 2 citations
Medicine · Pharmacology, Toxicology and Pharmaceutics · Chemistry · #Cancer Treatment and Pharmacology #Alkaloids: synthesis and pharmacology #Carbohydrate Chemistry and Synthesis
paper · doi:10.1021/jm801064y
openalex publication_date 2008/12/12 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
Ten hybrids of vinca alkaloids and phomopsin A have been synthesized by linking the octahydrophomopsin lateral chain to the tertiary amine of the cleavamine moiety of anhydrovinblastine (AVLB) and vinorelbine. These compounds have been elaborated in order to obtain original products that may interfere with both binding sites of vinblastine (VLB) and phomopsin in tubulin. Although NMR and molecular modeling studies have shown that the orientation of the added peptide chains of these hybrids is not the same as those of phomopsin A, most of them are very potent inhibitors of microtubules assembly and they present good cytotoxicity against KB cell line. These interesting biological activities may eventually be explained by the fact that their lateral chain resides in a pocket distinct from that of the phomopsin A peptide, at the interface of tubulins beta and alpha.