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Design and Synthesis of Pro-Apoptotic Compounds Inspired by Diatom Oxylipins
Stazione Zoologica Anton Dohrn, Napoli 80121, Italy
Institute of Biomolecular Chemistry, National Research Council, Pozzuoli 80078, Italy
Institute of Food Sciences, National Research Council, Avellino 83100, Italy
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 5 September 2013; in revised form: 29 October 2013 / Accepted: 1 November 2013 / Published: 13 November 2013
Abstract: Oxylipins are a large and diverse family of fatty acid derivatives exhibiting different levels of oxidation of the carbon chain. They are involved in many biological functions in mammals, plants and diatoms. In this last group of organisms, they are suggested to play a role in the reproductive failure of copepod predators, showing clear pro-apoptotic effects on newborn nauplii. In this work, these compounds were tested for the ability to induce mitotic arrest in sea urchin embryos. We show for the first time that oxylipins have an increased efficacy in their corresponding methylated form. Natural oxylipins were also used as an inspiration for the rational design and synthesis of stable chemical analogs with apoptotic activity against tumor cell lines. This approach led to the synthesis of the linear C15-ketol (22) that was shown to induce apoptosis in human leukemia U-937 cells. These results are proof of the concept of the use of eco-physiological considerations as a platform to guide the search for novel drug candidates.
Keywords: diatoms; oxylipins; chemical synthesis; bioactivity; apoptosis
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Romano, G.; Manzo, E.; Russo, G.L.; d'Ippolito, G.; Cutignano, A.; Russo, M.; Fontana, A. Design and Synthesis of Pro-Apoptotic Compounds Inspired by Diatom Oxylipins. Mar. Drugs 2013, 11, 4527-4543.
Romano G, Manzo E, Russo GL, d'Ippolito G, Cutignano A, Russo M, Fontana A. Design and Synthesis of Pro-Apoptotic Compounds Inspired by Diatom Oxylipins. Marine Drugs. 2013; 11(11):4527-4543.
Romano, Giovanna; Manzo, Emiliano; Russo, Gian L.; d'Ippolito, Giuliana; Cutignano, Adele; Russo, Maria; Fontana, Angelo. 2013. "Design and Synthesis of Pro-Apoptotic Compounds Inspired by Diatom Oxylipins." Mar. Drugs 11, no. 11: 4527-4543.