Biseokeaniamides A, B, and C, Sterol O-Acyltransferase Inhibitors from an Okeania sp. Marine Cyanobacterium

Abstract

Biseokeaniamides A, B, and C (1-3), structurally novel sterol O-acyltransferase (SOAT) inhibitors, were isolated from an Okeania sp. marine cyanobacterium. Their structures were elucidated by spectroscopic analyses and degradation reactions. Biseokeaniamide B (2) exhibited moderate cytotoxicity against human HeLa cancer cells, and compounds 1-3 inhibited both SOAT1 and SOAT2, not only at an enzyme level but also at a cellular level. Biseokeaniamides (1-3) are the first linear lipopeptides that have been shown to exhibit SOAT-inhibitory activity.

Structural Diversity, Biological Properties and Applications of Natural Products from Cyanobacteria. A Review

“…Thiazole containing lipopeptides, biseokeaniamides A–C ( 47 – 49 ), were identified and purified from the Japanese cyanobacterial Okeania sp. [ 59 ]. Biseokeaniamide A consisted of five amino acid residues including two methyl valines ester, methyl phenylalanine ester, proline, and leucine with a thiazole ring N -methyl-2-thiazolemethane-amine (Thz- N -Me-Gly) and butanoic acid (Ba).…”

Marine Cyanobacteria: A Source of Lead Compounds and their Clinically-Relevant Molecular Targets

“…The range of molecules presented in this review is by no means exhaustive, as there are numerous potent cyanobacterial compounds reported in the literature and are beyond the scope of this review. These compounds include the highly cytotoxic compounds, bisebromoamide (65) and aurilide-class of compounds (e.g., 66), antiinfective molecules, almiramides (e.g., 67) and janadolide (68), anti-inflammatory molecule, biseokeaniamide A (69) as well as cannabimimetics/CNS modulatory agents, such as mooreamide A and serinolamides (e.g., 70) (Figure 13) [145][146][147][148][149][150][151][152][153]. Further biological evaluation and synthesis of analogues have also been initiated for some of these compounds [154][155][156][157][158][159].…”

Total synthesis of biseokeaniamides A–C and late-stage electrochemically-enabled peptide analogue synthesis

“…Importantly, spectral data for the three compounds is fully consistent with that reported for the original isolates (see ESI †). 5 Devising a strategy for C-terminal modication Although our optimized methods enabled robust access to the natural products, the inability to fully suppress epimerization in the coupling of the terminal thiazole was a powerful motivation for further exploration of late-stage installation protocols which would circumvent the need for peptide extension in the N-to Cdirection. Existing syntheses of C-terminal thiazole-containing natural products have largely exploited building block approaches, particularly in cases where the thiazole component bears dened a-chirality.…”

“…Isolated from Okeania sp. cyanobacterium in 2017, 5 these lipopeptides feature an intriguing C-terminal thiazole motif as well as an N-terminal lipid chain and a heavily N-methylated backbone. The analogues vary only in their pattern of N-methylation, thus offering additional opportunities for probing the effects of Nmethylation on peptide conformation and hydrophobicity, Scheme 1 (A) The biseokeaniamide natural products; (B) an electrochemical approach to late-stage peptide modification for the rapid synthesis of natural product analogues.…”