Phyllofenones F–M, Scalarane Sesterterpenes from the Marine Sponge Phyllospongia foliascens

Eight new scalarane sesterterpenes, phyllofenones F–M (1–8), together with two known analogues, carteriofenones B and A (9–10), were isolated from the marine sponge Phyllospongia foliascens collected from the South China Sea. The structures of these compounds were determined based on extensive spectroscopic and quantum chemical calculation analysis. The antibacterial and cytotoxic activity of these compounds was evaluated. Among them, only compounds 4 and 6 displayed weak inhibitory activity against Staphylococcus aureus and Escherichia coli, with MIC values of 16 μg/mL and 8 μg/mL, respectively. Compounds 1–10 exhibited cytotoxic activity against the HeLa, HCT-116, H460, and SW1990 cancer cell lines, with IC50 values ranging from 3.4 to 19.8 μM.

The cytotoxic activity of compounds 1-10 was tested against HeLa, HCT-116, H460, and SW1990 by the CCK-8 method.Among them, only compound 5 exhibited significant cytotoxic activity against the above cancer cell lines, with IC50 values ranging from 3.4 to 7.3 µM (Table 4).Comparing the relative potency of these scalaranes revealed that the substitution of a 4-methylpentanoate group at C-12 increased the cytotoxicity compared to a valerate group at C-12.This observation is consistent with previously reported results [4].Additionally, the α-OH substitution at C-16 in 4, compared to the β-OH substitution at C-16 in 6, led to increased cytotoxic activity.Furthermore, these derivatives were also assayed for antibacterial activity against Vibrio parahaemolyticus, V. alginolyticus, V. cholerae, V. vulnificus, Staphylococcus aureus, and Escherichia coli by the minimum inhibitory concentration (MIC) method.Only compounds 4 and 6 displayed weak activity against S. aureus and E. coli, with MIC values of 16 µg/mL and 8 µg/mL, respectively.The known compounds carteriofenones B and A (9-10) were also isolated from P. foliascens and were completely characterized via a comparison of their NMR data with those previously reported [18].
The cytotoxic activity of compounds 1-10 was tested against HeLa, HCT-116, H460, and SW1990 by the CCK-8 method.Among them, only compound 5 exhibited significant cytotoxic activity against the above cancer cell lines, with IC 50 values ranging from 3.4 to 7.3 µM (Table 4).Comparing the relative potency of these scalaranes revealed that the substitution of a 4-methylpentanoate group at C-12 increased the cytotoxicity compared to a valerate group at C-12.This observation is consistent with previously reported results [4].Additionally, the α-OH substitution at C-16 in 4, compared to the β-OH substitution at C-16 in 6, led to increased cytotoxic activity.Furthermore, these derivatives were also assayed for antibacterial activity against Vibrio parahaemolyticus, V. alginolyticus, V. cholerae, V. vulnificus, Staphylococcus aureus, and Escherichia coli by the minimum inhibitory concentration (MIC) method.Only compounds 4 and 6 displayed weak activity against S. aureus and E. coli, with MIC values of 16 µg/mL and 8 µg/mL, respectively.

Biological Assays
The cytotoxicity of compounds 1-10 against the HeLa, HCT-116, H460, and SW1990 human cancer cell lines was determined using the CCK-8 method [4,20], with cisplatin used as a positive control.The antimicrobial activity of compounds 1-10 against Vibrio parahaemolyticus, V. alginolyticus, V. cholerae, V. vulnificus, Staphylococcus aureus, and Escherichia coli was evaluated as previously described [4], with levofloxacin used as a positive control.

Conclusions
Eight new scalarane sesterterpenes, phyllofenones F-M (1-8), along with two known analogues, carteriofenones B and A (9-10), were isolated from a South China Sea sponge, P. foliascens.In conjunction with our previous chemical study of the same organism, we discovered that a 4-methylpentanoate group substituted at C-12 positively affected the activity.Additionally, compound 5 displayed notable cytotoxicity, highlighting the significance of the α-OH substitution at C-16 for its cytotoxic properties.Collectively, this research contributes to the expansion of the chemical molecular diversity of the scalarane sesterterpene family.
5 in 1 to δ C 152.2 in 4, as well as the presence of an oxygenated methine (δ C 63.3, δ H 4.56) in 4 instead of the methylene (δ C 35.5, δ H 2.21) found in 1.These differences suggested the existence of a C-17/C-18 double bond in ring D with hydroxy substitution at C-16.Additional HMBC correlations from H-16 to C-17 and C-14, from H-18 to C-13, C-17, and C-24, and from H 3 -23 to C-13, C-14, and C-18, along with consecutive COSY correlations of H-14/H 2 -15/H-16, confirmed this hypothesis (Figure

Figure 6 .
Figure 6.Calculated and experimental ECD spectra of 6.Figure 6. Calculated and experimental ECD spectra of 6.

Figure 6 .
Figure 6.Calculated and experimental ECD spectra of 6.Figure 6. Calculated and experimental ECD spectra of 6.