A cytotoxic pentadecapeptide from a South African Didemnid tunicate

Gallegos, D; Serrill, J; Parker-Nance, Shirley; Dorrington, Rosemary A; Ishmael, J; McPhail, Kerry L

Title: A cytotoxic pentadecapeptide from a South African Didemnid tunicate
Creator: Gallegos, D, Serrill, J, Parker-Nance, Shirley, Dorrington, Rosemary A, Ishmael, J, McPhail, Kerry L
Date: 2016
Type: text
Type: article
Identifier: http://hdl.handle.net/10962/65935
Identifier: vital:28863
Identifier: https://doi.org/10.1055/s-0036-1596683
Description: publisher version
Description: The rate of discovery of new natural product chemical entities has plateaued, and unique populations of endemic, biologically diverse sessile marine organisms represent increasingly critical opportunities to discover new chemistry. Discovery of the mandelalides [1] as potent inhibitors of cancer cell growth from the new South African tunicate Lissoclinum mandelai is an example of the diverse suites of metabolites with potent biological activities that have been isolated from tunicates and other filter-feeding sessile marine organisms that house complex microbial consortia. Further investigation of archived and new tunicate collections from Algoa Bay, South Africa, has revealed a group of didemnid tunicates with an unusual gelatinous morphology similar to Lissoclinum mandelai. Using a bioassay-guided isolation approach, a new “gelatinous” species of the genus Didemnum has yielded a cytotoxic pentadecapeptide with a molecular mass of 1603.7688 Da, comprising fifteen residues including both proteinogenic and non-proteinogenic amino acids. The pure compound inhibited both HeLa cervical cancer and NCI-H460 non-small cell lung cancer cell lines when tested at 30 nM in preliminary assays against cells seeded at low densities. Inhibition of cancer cells at low starting density may be indicative of an anti-proliferative mechanism of action. The compound did not show antibacterial activity against Vibrio cholera. Didemnin B and its clinically approved analogue dehydrodidemnin B (plitidepsin, Aplidin®) [2, 3] are important macrocyclic depsipeptides from a didemnid tunicate. The pentadecapeptide reported here provides justification for our continued investigation of unique, endemic didemnid tunicates from South Africa as a source of new macrocyclic natural products with cytotoxic, anti-viral or antimicrobial activity.
Description: We acknowledge the South African government for permission to collect the subject tunicate (Collection Permit No. 278 RES2013/43)
Format: pdf
Publisher: Georg Thieme Verlag KG
Language: English
Relation: Planta Medica, Gallegos, D., Serrill, J., Parker-Nance, S., Dorrington, Rosemary A., Ishmael, J., McPhail, K.L. (2016) A cytotoxic pentadecapeptide from a South African Didemnid tunicate. Planta Medica, 82 (S 01): p.528.https://doi.org/10.1055/s-0036-1596683, Planta Medica volume 82 number S01 S628 S628 2016 0032-0943
Rights: Thieme Planta Medica
Rights: Use of this resource is governed by the terms and conditions of the National Library of South Africa Copyright Act (http://www.nlsa.ac.za/downloads/Copyright Act.pdf)

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Dorrington, Rosemary A (Prof)

RU DST/NRF SARChI for Marine Natural Products

RU DST/NRF SARChI for Marine Ecosystems and Resources

RU Department of Biochemistry, Microbiology and Bioinformatics

SDG 14. Life Below Water

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