Polyacetylene diols with antiproliferative and driving Th1 polarization effects from the marine sponge Callyspongia sp.

Abstract

A screening of 30 crude extracts of marine sponges against human promyelocytic leukemia cells (HL-60) yielded an EtOAc extract of the sponge Callyspongia sp. (Callyspongiidae) with significant activity. Further bioassay-guided fractionation of the EtOAc extract led to the isolation of three polyacetylene metabolites: a new polyacetylene diol, callyspongidiol (1), along with two known compounds, siphonodiol (2) and 14,15-dihydrosiphonodiol (3). Their structures were determined by a combination of spectroscopic analyses. Compounds 1-3 exhibited antiproliferative activity against HL-60 with IC(50) values of 6.5, 2.8, and 6.5 microg/ml, respectively. These metabolites induce apoptosis in HL-60 cells. Dendritic cells (DC) differentiated with 1-3 enhance the differentiation of naïve T cells towards the Th1 type.

Marine Polyacetylenes: Distribution, Biological Properties, and Synthesis

“…Further bioassay-guided fractionation of the EtOAc extract led to the isolation of three polyacetylene metabolites: callyspongidiol (28A) [42], siphonodiol (28B), and 14,15-dihydrosiphonodiol (28C) [43]. showed significant activity against human promyelocytic leukemia cells (HL-60).…”

“…The 1,5-dien-3-yne ether lipid raspailynes (42) have been isolated from Raspailia pumila and Raspailia ramosa (order Axinellida) [54]. The enol double bond is conjugated to both acetylenic and olefinic bonds.…”

Polyacetylenediols regulate the function of human monocyte-derived dendritic cells

“…LPS from Escherichia coli were purchased from Sigma-Aldrich Callyspongidiol and 14,15-dihydrosiphonodiol ( Fig. 1) were prepared as previously described [17]. The purity of callyspongidiol and 14,15-dihydrosiphonodiol was N99%.…”

“…Siphonodiol and two related metabolites from siphonochalina truncata have been shown to inhibit H+, K+-ATPase [19]. Furthermore, callyspongidiol and 14,15-dihydrosiphonodiol exhibited antiproliferative activity against HL-60 [17]. We have recently reported that siphonodiol differentiated human monocytes DC and siphonodiol-primed DC induced the differentiation of naïve T cells towards Th1 response [20].…”

“…(Callyspongiidae) [17]. Polyacetylenes have been identified as a unique class of natural products possessing diverse biological activities.…”