Pederin is a

vesicant A blister agent (or vesicant), is a chemical compound that causes severe skin, eye and mucosal pain and irritation. They are named for their ability to cause severe chemical burns, resulting in painful water blisters on the bodies of those affec ...

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...

with two

tetrahydropyran Tetrahydropyran (THP) is the organic compound consisting of a saturated six-membered ring containing five carbon atoms and one oxygen atom. It is named by reference to pyran, which contains two double bonds, and may be produced from it by addin ...

rings, found in the

haemolymph Hemolymph, or haemolymph, is a fluid, analogous to the blood in vertebrates, that circulates in the interior of the arthropod (invertebrate) body, remaining in direct contact with the animal's tissues. It is composed of a fluid plasma in which ...

of the beetle genus ''

Paederus ''Paederus'' is a genus of small beetles of the family Staphylinidae ("rove beetles"). With 622 valid species assigned by 1987 to the subtribe Paederina (''Paederus'' and its close allies), and with all but 148 within ''Paederus'' itself, the ge ...

'', including the

Nairobi fly Nairobi fly is the common name for two species of rove beetle in the genus ''Paederus,'' native to East Africa. The beetles contain a corrosive substance known as pederin, which can cause chemical burns if it comes into contact with skin. Becaus ...

, belonging to the family

Staphylinidae The rove beetles are a family (Staphylinidae) of beetles, primarily distinguished by their short elytra (wing covers) that typically leave more than half of their abdominal segments exposed. With roughly 63,000 species in thousands of genera, the ...

. It was first characterized by processing 25 million field-collected ''P. fuscipes''.Bugs Don’t Have to Bite to Do Damage:The Tale of the Paederus Beetle
It makes up approximately 0.025% of an insects weight (for ''P. fuscipes''). It has been demonstrated that the production of pederin relies on the activities of an

endosymbiont An ''endosymbiont'' or ''endobiont'' is any organism that lives within the body or cells of another organism most often, though not always, in a mutualistic relationship. (The term endosymbiosis is from the Greek: ἔνδον ''endon'' "within" ...

(''

Pseudomonas ''Pseudomonas'' is a genus of Gram-negative, Gammaproteobacteria, belonging to the family Pseudomonadaceae and containing 191 described species. The members of the genus demonstrate a great deal of metabolic diversity and consequently are able ...

ssp.'') within ''Paederus''. The manufacture of pederin is largely confined to adult female beetles—larvae and males only store pederin acquired maternally (i.e., through eggs) or by ingestion.

Physical effects

Skin contact with pederin from the coelomic fluid exuded from a female Paederus beetle causes

Paederus dermatitis Paederus dermatitis, medically known as dermatitis linearis, is a skin irritation resulting from contact with the hemolymph of certain rove beetles, a group that belongs to the insect order Coleoptera and the genus ''Paederus''. Other local nam ...

. This is a rash that varies from a slight erythema to severe blistering, depending on the concentration and duration of exposure. Treatment involves washing the irritated area with cool soapy water. Application of a topical steroid is also recommended for more intense exposures.Paederus Dermatitis
/ref> These measures can significantly reduce the physical effects the toxin has on the affected area. Paederus littoralis December 2016-1

Synthesis

An efficient total synthesis of pederin is known. Beginning with (+)-benzoylselenopederic acid, Zn(BH₄)₂ reduction is applied, introducing stereoselective reduction of the acyclic ketone.

Michael addition In organic chemistry, the Michael reaction or Michael addition is a reaction between a Michael donor (an enolate or other nucleophile) and a Michael acceptor (usually an α,β-unsaturated carbonyl) to produce a Michael adduct by creating a carbon ...

nitromethane Nitromethane, sometimes shortened to simply "nitro", is an organic compound with the chemical formula . It is the simplest organic nitro compound. It is a polar liquid commonly used as a solvent in a variety of industrial applications such as in ...

is performed. After several steps of

Moffatt oxidation Moffat is a former burgh and spa town in Dumfries and Galloway, Scotland. Moffat or Moffatt may also refer to: Places United States * Moffat, Colorado, a town * Moffat County, Colorado * Moffat Tunnel, a railroad tunnel in Colorado * Moffatt Tow ...

, phenylselenation, hydrolysis, and reduction, pederic acid is reached. The final steps of the synthesis of pederin are shown to the right. Here, pederic acid is added to the protected compound in LiHMDS and THF, producing a 75% yield. The protecting groups are then removed using TBAF and a hydrolytic quench. This step gives an 88% yield. Pederin Synthesis

Mode of action

Pederin blocks

mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...

at levels as low as 1 ng/ml, by inhibiting protein and DNA synthesis without affecting RNA synthesis, prevents cell division, and has been shown to extend the life of mice bearing a variety of tumors. For these reasons, it has garnered interest as a potential anti-

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

treatment.

Uses

Pederin and its derivatives are being researched as anticancer drugs. This family of compounds is able to inhibit protein and DNA biosynthesis, making it useful to slow the division of cancer cells. One derivative of pederin, psymberin, has been found to be highly selective in targeting solid tumor cells.

References

{{Reflist Acetamides Ethers Tetrahydropyrans Blister agents

Physical effects

Synthesis

Mode of action

Uses

See also

References