Pharmaceutical design of antimitotic agents based on combretastatins.
The design of novel anticancer agents based on the combretastatins, a group of antimitotic agents isolated from the bark of the South African willow tree Combretum caffrum Kuntz, is of considerable contemporary interest. Combretastatin A-4, the most active compound in the group, due to its unique dual features of antitubulin and antivascular properties, has drawn significant attention of medicinal chemists for the design of analogues as novel antitumor agents. To date, 252 references have been published since 1982 and 187 references have been published since 1998 related to combretastatins research. The 102 references related to chemistry efforts can be classified into three different categories including one-atom, two-atom, and three-atom bridgeheads as linker between two aryl rings of combretastatins. This review will particularly elucidate the rationale and strategic tactics towards the development of novel classes of antimitotic agents, based upon combretastatin A-4 as a promising lead.
Hsieh
H P
HP
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Taipei, Taiwan, Republic of China. hphsieh@nhri.org.tw
Liou
J P
JP
Mahindroo
N
N
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001632:Bibenzyls / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015195:Drug Design; D006801:Humans; D013267:Stilbenes / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001632:Bibenzyls; D013267:Stilbenes; C040105:combretastatin