Phenylahistin Explained

Phenylahistin is a metabolite produced by the fungus Aspergillus ustus^[1] that belongs to a class of naturally occurring 2,5-diketopiperazines featuring a dehydrohistidine residue that exhibit important biological activities, such as anti-cancer or neurotoxic effects.^[2]

Phenylahistin is a microtubule binding agent that exhibits cytotoxic activities against a wide variety of tumor cell lines.^[3] A series of synthetic analogs were prepared to remove the chirality and optimize biological activity. These studies led to the potent anti-tumor agent plinabulin, which is active in multidrug-resistant (MDR) tumor cell lines.^[4]

Notes and References

1. (−)-Phenylahistin: A new mammalian cell cycle inhibitor produced by aspergillus ustus. Kanoh K, Kohno S, Asari T, Harada T, Katada J, Muramatsu M, Kawashima H, Sekiya H, Uno I . Bioorganic & Medicinal Chemistry Letters . 1997 . 7 . 22 . 2847–2852 . 10.1016/S0960-894X(97)10104-4.
2. 2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products . Borthwick AD . Chemical Reviews . 2012 . 112 . 7 . 3641–3716 . 10.1021/cr200398y . 22575049.
3. Antitumor activity of phenylahistin in vitro and in vivo.. Kanoh K, Kohno S, Katada J, Hayash Y, Muramatsu M, Uno I . Bioscience, Biotechnology, and Biochemistry . 1999 . 63 . 6 . 1130–1133. 10.1271/bbb.63.1130 . 10427703. free .
4. NPI-2358 is a tubulin-depolymerizing agent: in-vitro evidence for activity as a tumor vascular-disrupting agent . Nicholson B, Lloyd GK, Miller BR, Palladino MA, Kiso Y, Hayashi Y, Neuteboom ST . Anticancer Drugs . 2006 . 17 . 1 . 25–31. 10.1097/01.cad.0000182745.01612.8a . 16317287. 33272285 .