Eudistomin

Eudistomins are β-carboline derivatives, isolated from ascidians (marine tunicates of the family Ascidiacea), like Ritterella sigillinoides,^[1] Lissoclinum fragile,^[2] or Pseudodistoma aureum.^[3][4]

Eudistomins

Types of Eudistomin

Eudistomin C

Eudistomin C is a naturally occurring β-carboline derivative which has been found in the Ascidian, Eudistoma Olivaseum. Eudistomin C is a cytotoxic molecule; this cytotoxicity is achieved by the Eudistomin C binds onto the 40S or 80S Ribosomal subunits, which inhibits the process of protein translation, leading to cell death. There are cells that are resistance to Eudistomin C's cytotoxicity, and these cells are called Yeast EudiC Resistance mutants (YER). YER mutants have a RPS14A mutation on the cell's uS11 gene, which encodes for the cell's 40S ribosomal subunit. This produces the RPS14A 40S Ribosomal subunit which confers a resistance against Eudistomin C, preventing protein translation inhibition. Eudistomin C has also shown antitumor and antiviral properties. The exact mechanism of these properties are unknown, however it is believed that its ability to inhibit protein translation is responsible for its antitumor and antiviral properties.^[5]

Eudistomin U

Eudistomin U is a β-carboline derivative. The structure of this molecule is made up of a β-carboline with an aromatic indole at the 1' position, thus also functioning as an indole.^[6] Eudistomin C is also a cytotoxic molecule, and its cytotoxicity have been shown to affect certain cancer cell line and human pathogens.^[7] A recent study suggested that this cytotoxicity may allow Eudistomin C to bind to DNA molecules. In addition to this, Eudistomin C displayed antibacterial property in Gram-Positive Bacteria. This is due to Eudistomin C damaging the bacteria's cell membrane and interfering with the DNA gyrase function, which directly leads to cell death.^[8][9]

References

1. Lake RJ, Blunt JW, Munro MH (1989). "Eudistomins From the New Zealand Ascidian Ritterella sigillinoides". Aust. J. Chem. 42 (7): 1201–1206. doi:10.1071/CH9891201.
2. Badre A, Boulanger A, Abou-Mansour E, Banaigs B, Combaut G, Francisco C (April 1994). "Eudistomin U and Isoeudistomin U, New Alkaloids from the Caribbean Ascidian Lissoclinum fragile". J. Nat. Prod. 57 (4): 528–533. doi:10.1021/np50106a016. PMID 8021654.
3. Ohizumi, Yasushi; Matsunaga, Kimihiro; Nakatani, Keigo; Kobayashi, Jun′ichi (1998-05-01). "Potent Stimulation of Myofilament Force and ATPase Activity of Skeletal Muscle by Eudistomin M, a Novel Ca++-Sensitizing Agent from a Caribbean Tunicate". Journal of Pharmacology and Experimental Therapeutics. 285 (2): 695–699. ISSN 0022-3565. PMID 9580615.
4. Davis RA, Carroll AR, Quinn RJ (June 1998). "Eudistomin V, a New β-Carboline from the Australian Ascidian Pseudodistoma aureum". J. Nat. Prod. 61 (7): 959–960. doi:10.1021/np9800452. PMID 9677285.
5. Ota, Yu; Chinen, Takumi; Yoshida, Keisuke; Kudo, Shun; Nagumo, Yoko; Shiwa, Yuh; Yamada, Ryosuke; Umihara, Hirotatsu; Iwasaki, Kotaro; Masumoto, Hiroshi; Yokoshima, Satoshi (2016). "Eudistomin C, an Antitumor and Antiviral Natural Product, Targets 40S Ribosome and Inhibits Protein Translation". ChemBioChem. 17 (17): 1616–1620. doi:10.1002/cbic.201600075. ISSN 1439-7633. PMID 27304596. S2CID 11780141.
6. "Development of eudistomin U derivatives as novel DNA-binding agents". Retrieved 2021-04-27.
7. Roggero, Chad M.; Giulietti, Jennifer M.; Mulcahy, Seann P. (2014-08-01). "Efficient synthesis of eudistomin U and evaluation of its cytotoxicity". Bioorganic & Medicinal Chemistry Letters. 24 (15): 3549–3551. doi:10.1016/j.bmcl.2014.05.049. ISSN 0960-894X. PMC 4116134. PMID 24930832.
8. Dai, Jiangkun; Dan, Wenjia; Li, Na; Wang, Junru (2018-09-05). "Computer-aided drug discovery: Novel 3,9-disubstituted eudistomin U derivatives as potent antibacterial agents". European Journal of Medicinal Chemistry. 157: 333–338. doi:10.1016/j.ejmech.2018.08.001. ISSN 0223-5234. PMID 30099255. S2CID 51982156.
9. Giulietti, Jennifer M.; Tate, Patrick M.; Cai, Ang; Cho, Bongsup; Mulcahy, Seann P. (2016-10-01). "DNA-binding studies of the natural β-carboline eudistomin U". Bioorganic & Medicinal Chemistry Letters. 26 (19): 4705–4708. doi:10.1016/j.bmcl.2016.08.047. ISSN 1464-3405. PMC 5018459. PMID 27567367.

Further reading

• Edrada-Ebel, RuAngelie; Schupp, Paul R (2003). "Eudistomins W and X, Two New β-Carbolines from the Micronesian Tunicate Eudistoma sp". Journal of Natural Products. 66 (2): 272–275. doi:10.1021/np020315n. PMID 12608864.
• Rinehart, Kenneth L.; Kobayashi, Jun'ichi; Harbour, Gary C.; Gilmore, Jeremy; Mascal, Mark; Holt, Tom G.; Shield, Lois S.; Lafargue, Françoise (1987). "Eudistomins A-Q, β-carbolines from the antiviral Caribbean tunicate Eudistoma olivaceum". Journal of the American Chemical Society. 109 (11): 3378–3387. doi:10.1021/ja00245a031. ISSN 0002-7863.