Piscarinines are bioactive alkaloid isolates of Penicillium piscarium NKM F-961 [1] and Penicillium piscarium Westling [2] that belong to a class of naturally occurring 2,5-diketopiperazines. [3] The cytotoxic dehydroproline tryptophan derivatives piscarinines A and B were shown to be active against the prostate cancer cell line LNCAP [2] (IC50 values were 2.2 and 1.9 μg/mL for piscarinine A and B, respectively).
Gliotoxin is a sulfur-containing mycotoxin that belongs to a class of naturally occurring 2,5-diketopiperazines produced by several species of fungi, especially those of marine origin. It is the most prominent member of the epipolythiopiperazines, a large class of natural products featuring a diketopiperazine with di- or polysulfide linkage. These highly bioactive compounds have been the subject of numerous studies aimed at new therapeutics. Gliotoxin was originally isolated from Gliocladium fimbriatum, and was named accordingly. It is an epipolythiodioxopiperazine metabolite.
Spirotryprostatin B is an indolic alkaloid found in the Aspergillus fumigatus fungus that belongs to a class of naturally occurring 2,5-diketopiperazines. Spirotryprostatin B and several other indolic alkaloids have been found to have anti-mitotic properties, and as such they have become of great interest as anti-cancer drugs. Because of this, the total syntheses of these compounds is a major pursuit of organic chemists, and a number of different syntheses have been published in the chemical literature.
Spirotryprostatin A is an indolic alkaloid from the 2,5-Diketopiperazine class of natural products found in the Aspergillus fumigatus fungus. Spirotryprostatin A and several other indolic alkaloids have been found to have anti-mitotic properties, and as such they have become of great interest as anti-cancer drugs. Because of this, the total syntheses of these compounds is a major pursuit of organic chemists, and a number of different syntheses have been published in the chemical literature.
Roquefortine C is a mycotoxin that belongs to a class of naturally occurring 2,5-diketopiperazines produced by various fungi, particularly species from the genus Penicillium. It was first isolated from a strain of Penicillium roqueforti, a species commercially used as a source of proteolytic and lipolytic enzymes during maturation of the blue-veined cheeses, Roquefort, Danish Blue, Stilton and Gorgonzola.
Brevianamides are indole alkaloids that belong to a class of naturally occurring 2,5-diketopiperazines produced as secondary metabolites of fungi in the genus Penicillium and Aspergillus. Structurally similar to paraherquamides, they are a small class compounds that contain a bicyclo[2.2.2]diazoctane ring system. One of the major secondary metabolites in Penicillium spores, they are responsible for inflammatory response in lung cells.
2,5-Diketopiperazine, also known as piperazine-2,5-dione and as the cyclodipeptide cyclo(Gly-Gly), is an organic compound and the smallest possible cyclic peptide - it is a six-membered ring containing two amide linkages where the two nitrogen atoms and the two carbonyls are at opposite positions in the ring. It was first synthesized by Curtius and Gloebel in 1888 and was the first compound containing a peptide bond to be studied by X-ray crystallography in 1938. It occurs in cocoa and bread and has a metallic and bitter taste.
A diketopiperazine (DKP), also known as a dioxopiperazine or piperazinedione, is a class of organic compounds related to piperazine but with two amide linkages. Three regioisomers are possible, differing in the locations of the carbonyl groups.
(−)-Aurantiamine is a blue fluorescence metabolite produced by the fungus Penicillium aurantiogriseum, the most common fungi found in cereals. (−)-Aurantiamine 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. It is the isopropyl analog of the microtubule binding agent (−)-phenylahistin but is 40 times less active than the latter on P388 cell proliferation. The total asymmetric synthesis of (−)-aurantiamine has been described.
Fumitremorgins are tremorogenic metabolites of Aspergillus and Penicillium, that belong to a class of naturally occurring 2,5-diketopiperazines.
Fellutanine A, B, C and D are bio-active diketopiperazine alkaloids isolated from the cultures of Penicillium fellutanum, that belongs to a class of naturally occurring 2,5-diketopiperazines. Originally they were thought to be based on the "trans" cyclic dipetide cyclo(L-Trp-D-Trp) but were later shown to be based on the "cis" cyclic dipetide cyclo(L-Trp-L-Trp). This was also confirmed when fellutanine A, B and C were isolated from Penicillium simplicissimum. The fellutanines A−C, are non-annulated analogues of cyclo(L-Trp-L-Trp), but unlike their diannulated analogue fellutanine D are not cytotoxic.
Verruculogen is a mycotoxin produced by certain strains of aspergillus that belongs to a class of naturally occurring 2,5-diketopiperazines. It is an annulated analogue of cyclo(L-Trp-L-Pro) which belongs to the most abundant and structurally diverse class of tryptophan-proline 2,5-diketopiperazine natural products. It produces tremors in mice due to its neurotoxic properties. It also tested positive in a Salmonella/mammalian microsome assay and was shown to be genotoxic. It is a potent blocker of calcium-activated potassium channels.
Akuammicine is a monoterpene indole alkaloid of the Vinca sub-group. It is found in the Apocynaceae family of plants including Picralima nitida, Vinca minor and the Aspidosperma.
Rugulosuvines are bio-active alkaloids made by Penicillium, that belongs to a class of naturally occurring 2,5-diketopiperazines.
Stephacidin A and B are antitumor alkaloids isolated from the fungus Aspergillus ochraceus that belong to a class of naturally occurring 2,5-diketopiperazines. This unusual family of fungal metabolites are complex bridged 2,5-diketopiperazine alkaloids that possess a unique bicyclo[2.2.2]diazaoctane core ring system and are constituted mainly from tryptophan, proline, and substituted proline derivatives where the olefinic unit of the isoprene moiety has been formally oxidatively cyclized across the α-carbon atoms of a 2,5-diketopiperazine ring. The molecular architecture of stephacidin B, formally a dimer of avrainvillamide, reveals a complex dimeric prenylated N-hydroxyindole alkaloid that contains 15 rings and 9 stereogenic centers and is one of the most complex indole alkaloids isolated from fungi. Stephacidin B rapidly converts into the electrophilic monomer avrainvillamide in cell culture, and there is evidence that the monomer avrainvillamide interacts with intracellular thiol-containing proteins, most likely by covalent modification.
Dideoxyverticillin A, also known as (+)-11,11′-dideoxyverticillin A, is a complex epipolythiodioxopiperazine initially isolated from the marine fungus Penicillium sp. in 1999. It has also been found in the marine fungus Bionectriaceae, and belongs to a class of naturally occurring 2,5-diketopiperazines.
Fungal isolates have been researched for decades. Because fungi often exist in thin mycelial monolayers, with no protective shell, immune system, and limited mobility, they have developed the ability to synthesize a variety of unusual compounds for survival. Researchers have discovered fungal isolates with anticancer, antimicrobial, immunomodulatory, and other bio-active properties. The first statins, β-Lactam antibiotics, as well as a few important antifungals, were discovered in fungi.
Penicillium thomii is an anamorph species of fungus in the genus Penicillium which was isolated from spoiled faba beans in Australia. Penicillium thomii produces hadicidine, 6-methoxymelline and penicillic acid
Penicillium vinaceum is an anamorph species of fungus in the genus Penicillium which produces penicillivinacine, vinaxanthone and citrmycetin.
Penicillium viridicatum is a psychrophilic species of fungus in the genus, penicillic acid and citrinin. Penicillium viridicatum can spoil grapes and melons.
Brevianamide F , also known as cyclo-(L-Trp-L-Pro), belongs to a class of naturally occurring 2,5-diketopiperazines. It is the simplest member and the biosynthetic precursor of a large family of biologically active prenylated tryptophan-proline 2,5-diketopiperazines that are produced by the fungi A. fumigatus and Aspergillus sp. It has been isolated from the bacterium Streptomyces sp. strain TN58 and shown to possess activity against the Gram-positive bacteria S. aureus and Micrococcus luteus. It has also been isolated from Bacillus cereus associated with the entomopathogenic nematode Rhabditis (Oscheius) sp. and shown to have antifungal activity against T. rubrum, C. neoformans, and C. albicans, better than amphotericin B. Although the proline 2,5-diketopiperazines are the most abundant and structurally diverse 2,5-diketopiperazines found in food, cyclo(L-Trp-L-Pro) has only been found as a minor 2,5-diketopiperazine (8.2 ppm) in autolyzed yeast extract. Initially, cyclo(L-Trp-L-Pro) and its DL, LD, and DD isomers showed potential for use in the treatment of cardiovascular dysfunction, but they were later shown to be hepatotoxic.