Design, synthesis and cytotoxic activities of naphthyl analogues of combretastatin A-4.
The 3,4,5-trimethoxyphenyl and 3-hydroxy-4-methoxyphenyl rings of combretastatin A-4 are deemed optimal for its activity as antimitotic agent. The replacement of either one by a naphthalene ring results in compounds with a potency comparable to that of the parent compound. These results show that the naphthalene ring is a good surrogate for the 3,4,5-trimethoxyphenyl or the 3-hydroxy-4-methoxyphenyl rings of combretastatin A-4 and that neither of them is essential for the antitumor activity.
Maya
A B
AB
Laboratorio de Química Orgáinica y Farmacéutica, Facultad de Farmacia, Universidad de Salamanca, Spain.
del Rey
B
B
Lamamie de Clairac
R P
RP
Caballero
E
E
Barasoain
I
I
Andreu
J M
JM
Medarde
M
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009281:Naphthalenes / Q000737:chemistry*; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009281:Naphthalenes; D013267:Stilbenes; C031721:naphthalene; C058728:fosbretabulin