Kalkipyrone B, a marine cyanobacterial γ-pyrone possessing cytotoxic and anti-fungal activities

Abstract

Bioassay-guided fractionation of two marine cyanobacterial extracts using the H-460 human lung cancer cell line and the OVC-5 human ovarian cancer cell line led to the isolation of three related α-methoxy-β, β’-dimethyl-γ-pyrones each containing a modified alkyl chain, one of which was identified as the previously reported kalkipyrone and designated kalkipyrone A. The second compound was an analog designated kalkipyrone B. The third was identified as the recently reported yoshipyrone A, also isolated from a marine cyanobacterium. Kalkipyrone A and B were obtained from a field-collection of the cyanobacterium Leptolyngbya sp. from Fagasa Bay, American Samoa, while yoshipyrone A was isolated from a field-collection of cyanobacteria (cf. Schizothrix sp.) from Panama. One-dimensional and two-dimensional NMR experiments were used to determine the overall structures and relative configurations of the kalkipyrones, and the absolute configuration of kalkipyrone B was determined by 1H NMR analysis of diastereomeric Mosher’s esters. Kalkipyrone A showed good cytotoxicity to H-460 human lung cancer cells (EC50 = 0.9 µM), w M), while kalkipyrone B and yoshipyrone A were less active (EC50 = 9.0 µM and > 10 µM, respectively). Both kalkipyrone A and B showed moderate toxicity to Saccharomyces cerevisiae ABC16-Monster strain (IC50 = 14.6 and 13.4 µM, respectively), whereas yoshipyrone A was of low toxicity to this yeast strain (IC50 = 63.8 µM).

Trichophycin A, a Cytotoxic Linear Polyketide Isolated from a Trichodesmium thiebautii Bloom

“…The number of free hydroxyl groups is critical to the antiproliferative effect of the macrocyclic polyketide amantelide A, as its peracetylated derivative was essentially inactive [ 9 ]. This effect was also observed with kalkipyrone B and its acetylated derivative [ 8 ]. These modified products have decreased hydroxyl character.…”

“…Macrocyclic and linear polyketides have been isolated from cyanobacteria with less regularity than NRPS and NRPS-PKS molecules. Still, many of these polyketides have exhibited a diverse array of biological activities [ 8 , 9 , 10 ] and possess highly functionalized structural elements [ 11 , 12 , 13 ] demonstrating the importance of their continued isolation and biological evaluation.…”

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

“…The latter consisted of three methyl groups, eleven methylenes, thirteen methines, and two quaternary carbon atoms with the presence of one aromatic ring. Trycophycin A showed several structural similarities to trichotoxin A and B [ 66 ] while possessing a longer polyketide chain than trichotoxin A with two additional alcohol groups and one additional branched methyl. Trichophycin A showed moderate cytotoxicity against neuro-2A cells and HCT-116 cells with EC 50 values 6.5 ± 1.4 μM and 11.7 ± 0.6 μM, respectively.…”

Saccharomonopyrones A–C, New α-Pyrones from a Marine Sediment-Derived Bacterium Saccharomonospora sp. CNQ-490

“…Pyrones are a well-known class of microbial secondary metabolites and are found to have a wide range of biological activities such as anti-inflammatory [ 9 ], anticancer [ 10 ], antimicrobial [ 11 , 12 ], anti-obesity [ 13 , 14 ], and antibiotic activities [ 15 ]. Previous studies on microbial sources have shown that the main producer of α-pyrones is fungi, but α-pyrones are also produced by plants, animals, and bacteria.…”