Phloroglucinol Derivatives from the Fruits of Eucalyptus globulus and Their Cytotoxic Activities

Abstract

A new phloroglucinol derivative, named eucalyptin B (1), along with five related known compounds (2 - 6), was isolated from the fruits of Eucalyptus globulus. Their structures were elucidated by means of 1D- and 2D-NMR spectroscopy, with the absolute configuration of 1 determined by electronic circular dichroism (ECD) calculations. All isolated compounds (1 - 6) were evaluated for their cytotoxic activities against lung (A549), breast (4T1), and skin (B16F10) cancer cell lines. On the basis of cell viability assay, the cytotoxic activity of eucalyptin B (1) was further confirmed by apoptosis assay. Additionally, after treatment with eucalyptin B (1), the apoptosis factor proteins (Bcl2 and Bax) and caspase-3 levels in A549 cells were also determined by Western-blot analysis. By cytotoxic assay, eucalyptin B (1) exhibited potent cytotoxicity against A549 cells with an IC value of 1.51 μm and induced concentration dependent apoptosis of up to 49%. Additionally, eucalyptin B (1) inhibited 5-fold and increased 10-folds in the level of Bcl2 and Bax, respectively. Furthermore, the 11-fold increase in the level of caspase-3 confirmed eucalyptin B (1) activated caspase dependent apoptosis pathway. In conclusion, the isolated compound eucalyptin B (1) has promising cytotoxic activity in tumor cells, especially in A549.

Eucalyptus globulus Labill. decoction extract inhibits the growth of NCI-H460 cells by increasing the p53 levels and altering the cell cycle profile

“…extract, a recent study has shown a promising cytotoxic effect of some phloroglucinol derivatives, isolated from the fruits of this species, in A549 (human lung cancer), 4 T1 (murine breast cancer), and B16F10 (murine myeloma) cell lines. 25 Therefore, the present study aimed to test the potential anti-cancer cell growth inhibitory effect of Eucalyptus globulus Labill. aqueous extracts, prepared by infusion and decoction, in three human tumor cell lines: the human colorectal adenocarcinoma HCT-15, the exocrine pancreatic cancer PANC-1 and the non-small cell lung cancer NCI-H460.…”

Structural Diversity of Complex Phloroglucinol Derivatives from Eucalyptus Species

“…Taxol, which was used as positive control, showed cytotoxicity at 4.1 μM against the same cell lines. In addition, western‐blot test confirmed that 22 induced apoptosis in A549 cell lines by caspase‐3 cascade activation [41] . Another investigation of E. globulus fruits led to the isolation of eucalyptins E−G ( 23 – 25 ).…”

“…In addition, western-blot test confirmed that 22 induced apoptosis in A549 cell lines by caspase-3 cascade activation. [41] Another investigation of E. globulus fruits led to the isolation of eucalyptins EÀ G (23 -25). These compounds were evaluated for their immunosuppressive effects and exhibited moderate inhibitory activities against lymph node cells with IC 50 values of 35.8, 26.3, and 35.3 μM, respectively.…”

Study on Chemical Constituents and Bioactivities from Eucalyptus globulus

“…[2,[7][8] Above-mentioned compounds 14 and 18 were isolated from the fruits of E. globulus for the first time. 16 compounds were isolated from the stem bark of E. globulus, named as β-amyrin (19), acetylursolic acid (20), acetyloleanolic acid (21), acetylbetulinic acid (22), erythrodiol (23), uvaol (24), 11α-methoxyacetylursolic acid methyl ester (25), betulinic acid methyl ester (26), cis-p-methoxy-cinnamoyloxyursolic acid methyl ester (27), cis-p-methoxy-cinnamoyl-oxyoleanolic acid methyl ester (28), ursolic acid methyl ester (29), methyl 3β,23-diacetoxy-12-ursen-28-oate (30), oleanolic acids (31), betulin (32), 2α,3α-isopropylidenedioxy-lup-20(29)-en-28oieaeid (33), 3β-formyloxyurs-11-en-28,13-olide (34). [24] Their structures are shown in Figure 2.…”

“…Pham et al [28] evaluated the cytotoxic activity of compound eucalyptin B (62), which exhibited potent cytotoxicity against A549 cells with an IC50 value of 1.51 µM and induced concentration dependent apoptosis of up to 49%. Compounds euglobal-V (70) and euglobal-III (71) exhibited moderate cytotoxic effects in A549 (29.9 and 13.8 µM), in 4T1 (18.77 and 8.45 µM), and in B16F10 (8.86 and 29.33 µM), respectively.…”