Fibrosterol Sulfates from the Philippine SpongeLissodendoryx(Acanthodoryx) fibrosa: Sterol Dimers that Inhibit PKCζ

Abstract

Three new sulfated sterol dimers, fibrosterol sulfates A−C (1−3), have been isolated from the sponge Lissodendoryx (Acanthodoryx) fibrosa, collected in the Philippines. The structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1 and 2 inhibited PKCζ with IC50 values of 16.4 and 5.6 μM, respectively.

Challenge of Large-Scale Motion for Residual Dipolar Coupling Based Analysis of Configuration: The Case of Fibrosterol Sulfate A

“…Configurations for the rigid steroid ring moieties were previously established on the basis of extensive 1D and 2D NMR experiments. 36 In this study we confirmed the configuration of steroid rings ABCD and A’B’C’D’ by comparing the similarity of the 1 D CH RDCs of parallel C–H vectors without calculation of the order tensor 16 since in the six-membered chair-like ring fragment of both steroid moieties [ABC/A’B’C’], all axial C–H bonds are parallel and therefore have nearly the same angle with respect to the alignment tensor. Thus, the 1 D CH couplings coming from axial C–H bonds within each of the steroid ring systems should have the same size, which is indeed the case (See Supporting Information, Table S2).…”

“…The structure of this compound (Figure 1) consists of two steroid parts whose relative and absolute configuration was determined by comparison of the chemical shifts of steroids of known absolute configuration and biosynthetic considerations. 36 The linker between the two steroid parts contains five additional stereocenters, of which C20 and C20’ were assigned again by biosynthetic considerations. As described in the Supporting Information, the configuration of these two stereocenters is corroborated by our RDC analysis.…”

Marine Pharmacology in 2009–2011: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action

“…In contrast, although a pharmacological activity was described, and an IC 50 for inhibition of an enzyme or receptor determined, detailed molecular mechanism of action studies were unavailable at the time of publication for the following 47 marine compounds included in Table 3: alotaketals A and B ( 183 , 184 ) [166]; aquastatin A ( 185 ) [167]; australin E ( 186 ) [168]; lyngbyastatins 9 & 10 ( 187 , 188 ) [169]; brunsvicamides A, B and C ( 189 – 191 ) [170]; carteriosulfonic acids A, B and C ( 192 – 194 ) [171]; Carteriospongia foliascens sesterterpenoids ( 195 , 196 ) [172]; clavatadines D and E ( 197 , 198 ) [173]; fibrosterol sulfates A and B ( 199 , 200 ) [174]; gracilin L ( 201 ) [175]; grassystatins A, B and C ( 141 – 143 ) [133]; 2-hydroxycircumdatin C ( 202 ) [176]; jaspaquinol ( 203 ) [177]; largamides A, B and C ( 204 – 206 ) [178]; largamide D oxazolidine ( 207 ) [179]; Laurencia similis brominated metabolites ( 208 , 209 ) [180]; molassamide ( 210 ) [181]; myrothenone A ( 211 ) [182]; 42-hydroxy-palytoxin ( 212 ) [183]; plectosphaeroic acids A, B and C ( 213 – 215 ) [184]; puupehenone ( 216 ) [177]; Sinularia numerosa oxylipin ( 217 ) [185]; sipholenone E ( 218 ) [186]; spartinoxide ( 219 ) [187]; 23- nor -spiculoic acid B ( 220 ) [188]; tanikolide dimer ( 221 ) [189]; tamulamides A and B ( 222 , 223 ) [190]; terretonins E and F ( 224 , 225 ) [191]; and tetrangulol methyl ether ( 226 ) [192]. …”

Monanchosterols A and B, Bioactive Bicyclo[4.3.1]steroids from a Korean Sponge Monanchora sp.

“…Monanchosterol A (1) 5.38,d (5.0) 4,6,8,9,14 120.5,CH 5.35,d (7.0) 4,6,8,9,14 8 145.0, C 147.5, C 9 57.6, CH 1.94,m 5,7,8,10,11 60.4,CH 1.92,m 7,8,10,11 10 49 . (12.5,6.3) 7,8,9,12,13,15,18 61.1,CH 2.15,dd (12.7,6.4) 7,8,9,12,13,15,18 15a 23 . …”

“…6 However, perhaps more significant than their diverse structures, the sponge-derived steroids exhibit a range of biological activities in a variety of therapeutic areas. 7 In the course of an ongoing program toward the isolation of biologically active metabolites from Korean marine organisms, a sponge of the genus Monanchora (class Demospongiae, order Poecilosclerida, family Crambeidae) was examined. 1 H NMRguided fractionation yielded three new steroids, monanchosterols A (1) and B (2) and compound 3.…”