Cytotoxic Sesquiterpenoid Quinones and Quinols, and an 11-Membered Heterocycle, Kauamide, from the Hawaiian Marine Sponge Dactylospongia elegans

Abstract

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.

Small Molecules of Marine Origin as Potential Anti-Glioma Agents

“…Sesquiterpene 30-38 (Figure 14) were isolated from the extracts of the Hawaiian marine sponge Dactylospongia elegans. These nine compounds showed strong to moderate cytotoxicity (IC 50 values of 2.4-19.4 µM) against the human glioma cancer cell line, U251MG (Table 1) [53]. Compound 39 was isolated from a marine sponge Haliclona tubifera, which is abundant species on the southern Brazilian coast (Figure 15).…”

“…Sesquiterpene 30 – 38 ( Figure 14 ) were isolated from the extracts of the Hawaiian marine sponge Dactylospongia elegans . These nine compounds showed strong to moderate cytotoxicity (IC 50 values of 2.4–19.4 μM) against the human glioma cancer cell line, U251MG ( Table 1 ) [ 53 ].…”

“… Sesquiterpenes 30 – 38 isolated from extracts of the Hawaiian marine sponge Dactylospongia elegans [ 53 ]. …”

Towards Knowledge Maintenance in Scientific Digital Libraries with the Keystone Framework

“…Support conformational analysis [9,22] "Conformational analysis of 4 was performed with Schrödinger MacroModel 2016 by following the method of Willoughby et al [35]." Successful example [53] "The successful characterization of karlotoxin 2 (KmTx2) followed by KmTx8 [17,28,33,40] "Therefore, we turned to a protocol that relies on density functional theory-based computations of 1H and 13C NMR chemical shifts and the use of statistical tools to assign the experimental data to the correct isomer of a compound [28]. "…”

“…The remaining four papers [17,28,33,40] stated that they used the WH protocol to calculate the theoretical NMR chemical shift and thus could be significantly impacted, because the theoretical NMR chemical shifts supported findings that went into abstracts or the conclusion section. We say "could be" because the nonreproducibility comes from the protocol's implementation rather than the protocol itself.…”