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.
Financial support came from Spanish DGICYT (SAF98-0103). R.P.L.C. thanks the Spanish Ministerio de Educación y Ciencia (MEC) for his ‘contrato de reincorporación’. Biological evaluation was supplied by Instituto Biomar S.L. (León, Spain).