Indolocarbazole

Indolocarbazoles (ICZs) are a class of compounds that are under current study due to their potential as anti-cancer as well as antimicrobial drugs and the prospective number of derivatives and uses found from the basic backbone alone.

Due to the extensive number of structures available, this review will focus on the more important groups here while covering their occurrence, biological activity, biosynthesis, and laboratory synthesis.

The first isolated ICZ, dubbed staurosporine (STA) was in 1977 from a culture of Streptomyces staurosporeus found in a soil sample from Iwate Prefecture, Japan.

Over the course of the next decade, further study of the compound showed some fungal inhibition, hypotensive activity, and most importantly, a broad protein kinase inhibitor.

Some of the strains from which ICZ compounds have been found are Actinomadura melliaura in Bristol Cove, San Diego County, California, Streptomyces hygroscopicus in Numazu Prefecture, Japan, Micromonospora sp.

In addition to actinomycetes, ICZs have been found in slime molds (myxomycetes), blue-green algae (cyanobacteria, and marine invertebrates.

Nostoc sphaericum from Manoa Hawaii, Tolypothrix tjipanasensis from Vero Beach, Florida, and Fischerella ambigua strain 108b from Leggingen, Switzerland.

[6] One of the major lessons learned from initial research on STA was the development of the pharmacophore model for a protein kinase inhibitor in which a bidentate hydrogen donating system flanked by various hydrophobic groups inserts into the binding site.

[8][9] Studies on Streptomyces griseus with in vitro protein labelling have led to inhibition of a wide range of cellular functions.

[21][22][23] A parallel pathway has been put forth for the structurally related disaccharide-substituted indolocarbazole AT2433, the aminopentose of which is also found appended to the 10-membered enediyne calicheamicin.

[27] Ever since the birth of ICZ research in the late seventies, the field has been burgeoning with continued advances in both technology and organic chemistry techniques.

While only a handful of ICZ based compounds have made it past stage II clinical trials, the sheer variety that these molecules can take on leaves much still unexplored territory.

Of particular recent interest in synthesis techniques is the use of palladium based catalysts, which have been found to be excellent activators for use in formation of carbon-carbon bonds.