Cytotoxic Sesquiterpenoid Quinones and Quinols, and an 11-Membered Heterocycle, Kauamide, from the Hawaiian Marine Sponge <i>Dactylospongia elegans</i>
Ram P. Neupane,
Stephen M. Parrish,
Jayanti Bhandari Neupane,
Wesley Y. Yoshida,
M. L. Richard Yip,
James Turkson,
Mary Kay Harper,
John D. Head,
Philip G. Williams
Affiliations
Ram P. Neupane
Department of Chemistry, University of Hawaii at Manoa, Honolulu, HI 96822, USA
Stephen M. Parrish
Department of Chemistry, University of Hawaii at Manoa, Honolulu, HI 96822, USA
Jayanti Bhandari Neupane
Department of Chemistry, University of Hawaii at Manoa, Honolulu, HI 96822, USA
Wesley Y. Yoshida
Department of Chemistry, University of Hawaii at Manoa, Honolulu, HI 96822, USA
M. L. Richard Yip
University of Hawaii Cancer Center, Honolulu, HI 96813, USA
James Turkson
University of Hawaii Cancer Center, Honolulu, HI 96813, USA
Mary Kay Harper
Department of Medicinal Chemistry, University of Utah, College of Pharmacy, Salt Lake City, UT 84112, USA
John D. Head
Department of Chemistry, University of Hawaii at Manoa, Honolulu, HI 96822, USA
Philip G. Williams
Department of Chemistry, University of Hawaii at Manoa, Honolulu, HI 96822, USA
Several known sesquiterpenoid quinones and quinols (1−9), and kauamide (10), a new polyketide-peptide containing an 11-membered heterocycle, were isolated from the extracts of the Hawaiian marine sponge Dactylospongia elegans. The planar structure of 10 was determined from spectroscopic analyses, and its relative and absolute configurations were established from density functional theory (DFT) calculations of the GIAO NMR shielding tensors, and advanced Marfey’s analysis of the N-MeLeu residue, respectively. Compounds 1 and 3 showed moderate inhibition of β-secretase 1 (BACE1), whereas 1−9 exhibited moderate to potent inhibition of growth of human glioma (U251) cells. Compounds 1−2 and 4−7 were also active against human pancreatic carcinoma (Panc-1) cells.
