Naphthalene combretastatin analogues: synthesis, cytotoxicity and antitubulin activity.
Synthesis and evaluation of new combretastatin analogues with varied modifications on the bridge and the aromatic rings, have shown that the 2-naphthyl moiety is a good surrogate for the 3-hydroxy-4-methoxyphenyl (B-ring) of combretastatin A-4. Other bicyclic systems, such as 6(7)-quinolyl and 5-indolyl, can replace the B-ring, but they produce less potent analogues in the cytotoxicity and tubulin polymerization inhibition assays. Other modifications are detrimental for the potency of the studied analogues. The 2-naphthyl combretastatin 53 and the related 6-quinolyl combretastatin 106 analogues are the most potent among the derivatives of this type, whereas 92 and 95 are the most potent among the naphthalene derivatives with a heterocycle in the bridge. Previous and new results in this family of combretastatin analogues are discussed.
Medarde
Manuel
M
Laboratorio de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain. medarde@usal.es
Maya
Ana B S
AB
Pérez-Melero
Concepción
C
D000818:Animals; D001632:Bibenzyls / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D001632:Bibenzyls; D009281:Naphthalenes; D013267:Stilbenes; D014404:Tubulin; D050257:Tubulin Modulators; C040105:combretastatin