Discovery and development of anticancer agents from marine sponges: perspectives based on a chemistry-experimental therapeutics collaborative program.
A collaborative program was initiated in 1990 between the natural product chemistry laboratory of Dr. Phillip Crews at the University of California Santa Cruz and the experimental therapeutics laboratory of Dr. Fred Valeriote at the Henry Ford Hospital in Detroit. The program focused on the discovery and development of anticancer drugs from sponge extracts. A novel in vitro disk diffusion, solid tumor selective assay was used to examine 2,036 extracts from 683 individual sponges. The bioassay-directed fractionation discovery component led to the identification of active pure compounds from many of these sponges. In most cases, pure compound was prepared in sufficient quantities to both chemically identify the active compound(s) as well as pursue one or more of the biological development components. The latter included IC50, clonogenic survival-concentration exposure, maximum tolerated dose, pharmacokinetics and therapeutic assessment studies. Solid tumor selective compounds included fascaplysin and 10-bromofascaplysin (Fascaplysinopsis), neoamphimedine, 5-methoxyneoamphimedine and alpkinidine (Xestospongia), makaluvamine C and makaluvamine H (Zyzzya), psymberin (Psammocinia and Ircinia), and ethylplakortide Z and ethyldidehydroplakortide Z (Plakortis). These compounds or analogs thereof continue to have therapeutic potential.
Josephine Ford Cancer Center, Division of Hematology and Oncology, Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, USA. Fvaleri1@hfhs.org
Frederick A
FA
Valeriote
Karen
K
Tenney
Joseph
J
Media
Halina
H
Pietraszkiewicz
Matthew
M
Edelstein
Tyler A
TA
Johnson
Taro
T
Amagata
Phillip
P
Crews
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003114:Colony-Forming Units Assay; D015507:Drugs, Investigational / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D013812:Therapeutics; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D000970:Antineoplastic Agents; D015507:Drugs, Investigational