Spongenolactones A–C, Bioactive 5,5,6,6,5-Pentacyclic Spongian Diterpenes from the Red Sea Sponge Spongia sp.

Abstract

Three new 5,5,6,6,5-pentacyclic spongian diterpenes, spongenolactones A–C (1–3), were isolated from a Red Sea sponge Spongia sp. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and the absolute configurations of 1–3 were determined on the basis of comparison of the experimental circular dichroism (CD) and calculated electronic circular dichroism (ECD) spectra. Compounds 1–3 are the first 5,5,6,6,5-pentacyclic spongian diterpenes bearing an β-hydroxy group at C-1. These metabolites were assayed for their cytotoxic, antibacterial, and anti-inflammatory activities. All three compounds were found to exert inhibitory activity against superoxide anion generation in fMLF/CB-stimulated human neutrophils. Furthermore, 1 showed a higher activity against the growth of Staphylococcus aureus in comparison to 2.

New 3,4-seco-3,19-Dinor- and Spongian-Based Diterpenoid Lactones from the Marine Sponge Spongia sp.

“…The 13 C NMR data of 1 displayed 18 carbon signals ( Table 1 ), which were assigned with the assistance of the 1 H and HSQC spectrum into three methyls (δ C 31.8, 21.4, and 19.5), six methylenes (δ C 44.2, 36.1, 22.2, 22.1, and 18.6, including one oxygenated methylene δ C 68.8), two methines (δ C 56.3 and 48.7) and seven non-protonated carbons (δ C 211.6, 174.3, 172.8, 171.2, 123.9, 40.2, and 37.6). In total, the NMR spectroscopic data of 1 ( Table 1 ) showed signals for an α,β-unsaturated γ -lactone (δ C 174.3, C; 171.2, C; 123.9, C and 68.8, CH 2 ; δ H 4.86, dt, J = 17.0, 2.5 Hz, 1H and 4.72, dd, J = 17.0, 2.5 Hz, 1H) [ 2 , 12 , 14 , 15 ]. Furthermore, the 1 H– 1 H COSY experiment showed the presence of two partial structures ( Figure 2 ), which were further connected by analysis of the HMBC correlations ( Figure 2 ), to establish the planar structure of 1 as 3,4- seco -3,19-dinorspongian diterpenoid lactone.…”

“…In the NOESY spectrum of compound 1 , the following NOE interactions were found ( Figure 3 ): H 3 -17 with H 3 -20, both H 3 -17 and H 3 -20 with one proton ( δ H 1.90) of H 2 -6 and one proton (δ H 1.65) of H 2 -11, and H 3 -17 with one proton (δ H 1.83) of H 2 -7 and one proton (δ H 4.86) of H 2 -15. The above finding revealed that these protons must be located in the same orientation and were assumed to be β protons [ 2 , 12 ]. In contrast, the NOE correlations of the H-7α (δ H 1.54) with both H-5 and H-9, and of H-9 with H-5 and H-12α (δ H 2.05), indicated that these protons must be positioned on the α-face [ 2 , 12 ].…”

“…The above finding revealed that these protons must be located in the same orientation and were assumed to be β protons [ 2 , 12 ]. In contrast, the NOE correlations of the H-7α (δ H 1.54) with both H-5 and H-9, and of H-9 with H-5 and H-12α (δ H 2.05), indicated that these protons must be positioned on the α-face [ 2 , 12 ]. Furthermore, a comparison of the experimental ECD spectrum with those calculated for 1a (5 R ,8 R ,9 R ,10 R - 1 ) and 1b (5 S ,8 S ,9 S ,10 S - 1 ) allowed us to conclude the 5 R ,8 R ,9 R ,10 R - configuration for 1 ( Figure 4 a).…”

“…The human hepatocellular carcinoma (HCC) Huh7 cells were used in the resazurin assay (Cayman Chemical) to evaluate the cytotoxicity of compounds ( Supplementary Table S13 ). The method was performed as described previously [ 18 , 19 ], and the detailed process of the cytotoxicity assay was the same as in our previous publications [ 12 , 25 ]. Sorafenib, the positive control, inhibited 52% of the growth of Huh7 cells at 12.5 µM, and the DMSO controls were assigned 100% of relative cell-viability.…”

“…Recently, we have reported the discovery of new spongian diterpenes, including four rare 5,5,6,6,5-pentacyclic diterpenoids, from a Red Sea sponge, Spongia sp. [ 12 , 13 ]. Some of these compounds have been shown to display antibacterial and anti-inflammatory activities.…”