Recent advances and limitations in the application of kahalalides for the control of cancer - 16/03/22

Doi : 10.1016/j.biopha.2022.112676

Scott Wyer ^a,^⁎ , Danyelle M. Townsend ^a, Zhiwei Ye ^a, Antonis Kourtidis ^b, Yeun-Mun Choo ^c, André Luís Branco de Barros ^d, Mohamed S. Donia ^e, Mark T. Hamann ^a

^a Department of Drug Discovery and Biomedical Science, College of Pharmacy, Medical University of South Carolina, Charleston 29425-5700, USA

^b Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA

^c Chemistry Department, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia

^d Department of Clinical and Toxicological Analyses, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil

^e Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA

^⁎ Corresponding author.

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Abstract

Since the discovery of the kahalalide family of marine depsipeptides in 1993, considerable work has been done to develop these compounds as new and biologically distinct anti-cancer agents. Clinical trials and laboratory research have yielded a wealth of data that indicates tolerance of kahalalides in healthy cells and selective activity against diseased cells. Currently, two molecules have attracted the greates level of attention, kahalalide F (KF) and isokahalalide F (isoKF, Irvalec, PM 02734, elisidepsin). Both compounds were originally isolated from the sarcoglossan mollusk Elysia rufescens but due to distinct structural characteristics it has been hypothesized and recently shown that the ultimate origin of the molecules is microbial. The search for their true source has been a subject of considerable research in the anticipation of finding new analogs and a culturable expression system that can produce sufficient material through fermentation to be industrially relevant.

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Keywords : 16SrRNA, Akt, Anti-psoriatic, Bryopsis , Cancer, Cytochrome c oxidase I, Cytotoxicity, Depsipeptide, Elisidepsin, ErbB, GLPORYx, Her2, Her3, Isokahalalide, Kahalalide A, Kahalalide G, Kahalalide, MAPK, Mollusk, Oncosis