Aristoforin, a novel stable derivative of hyperforin, is a potent anticancer agent.
Hyperforin, a natural product of St. John's wort (Hypericum perforatum L.), has a number of pharmacological activities, including antidepressive and antibacterial properties. Furthermore, hyperforin has pronounced antitumor properties against different tumor cell lines, both in vitro and in vivo. Despite being a promising novel anticancer agent, the poor solubility and stability of hyperforin in aqueous solution limits its potential clinical application. In this study, we present the synthesis of hyperforin derivatives with improved pharmacological activity. The synthesized compounds were tested for their solubility and stability properties. They were also investigated for their antitumor properties, both in vitro and in vivo. One of these hyperforin derivatives, Aristoforin, is more soluble in aqueous solution than hyperforin and is additionally highly stable. Importantly, it retains the antitumor properties of the parental compound without inducing toxicity in experimental animals. These data strongly suggest that Aristoforin has potential as an anticancer drug.
Gartner
Michael
M
Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig, Germany.
Müller
Thomas
T
Simon
Jan C
JC
Giannis
Athanassios
A
Sleeman
Jonathan P
JP
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D004355:Drug Stability; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D012995:Solubility; D013729:Terpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; C502222:Aristoforin; D001643:Bridged Bicyclo Compounds; D013729:Terpenes; D010696:Phloroglucinol; C001654:hyperforin