Structure elucidation, absolute configuration, and biological evaluation of cyclic peroxides from the sponge Plakinastrella sp

Rohitesh Kumar; Rhone K Akee; Lucero Martínez-Fructuoso; Vitor F Freire; Christopher C Thornburg; Jason R Evans; Brian D Peyser; Susan Ensel; Barry R O'Keefe; Tanja Grkovic

doi:10.1016/j.bmcl.2024.129963

Structure elucidation, absolute configuration, and biological evaluation of cyclic peroxides from the sponge Plakinastrella sp

Bioorg Med Chem Lett. 2024 Sep 14:113:129963. doi: 10.1016/j.bmcl.2024.129963. Online ahead of print.

Affiliations

¹ Natural Products Support Group, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702-1201, United States.
² Natural Products Branch, Developmental Therapeutic Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, MD 21702-1201, United States.
³ Natural Products Support Group, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702-1201, United States; Department of Chemistry and Physics, Hood College, Frederick, MD 21701-8599, United States.
⁴ Natural Products Branch, Developmental Therapeutic Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, MD 21702-1201, United States; Molecular Targets Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702-1201, United States. Electronic address: okeefeba@mail.nih.gov.
⁵ Natural Products Branch, Developmental Therapeutic Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, MD 21702-1201, United States; Molecular Targets Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702-1201, United States. Electronic address: tanja.grkovic@nih.gov.

PMID: 39278368
DOI: 10.1016/j.bmcl.2024.129963

Abstract

Two cyclic peroxides, plakortides V (1) and W (2) were purified from the organic extract of the sponge Plakinastrella sp. Their planar structures were established based on extensive NMR and MS analysis and the absolute configurations of the three stereogenic centers of the 1,2-dioxane moiety were determined to be 3R,4S,6S by comparative analysis of the ¹H NMR spectral data of the R- or S-MTPA Mosher esters. Compounds 1 and 2 exhibited potent cytotoxic activity against LOX IMVI (melanoma), UO-31 (renal), and HL-60 (TB) (leukemia) cell lines in the NCI-60 cytotoxicity assay.

Keywords: Absolute configuration; Cyclic peroxides; Marine natural products; NCI-60; Plakinastrella sp.; Plakortides.

Published by Elsevier Ltd.