Yeon-Ju Lee

Chromene induces apoptosis via caspase-3 activation in human leukemia HL-60 cells

In this study, the potent anti-tumor effects of brown algae on human leukemia HL-60 cells were investigated. The Sargassum siliquastrum extract among the 14 species of brown algae exhibited profound growth inhibitory effect on HL-60 cells in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, therefore, S. siliquastrum was selected for use in further experiments. The highest inhibitory activity of S. siliquastrum on HL-60 cells was detected in the chloroform fraction, and the active compound was identified as a kind of chromene, sargachromanol E (SE). SE treatment showed significant growth inhibitory effects on HL-60 cells in a dose-dependent manner by inducing apoptosis, as evidenced by the formation of apoptotic bodies, fragmented DNA ladder, and the accumulation of DNA in the sub-G(1) phase of cell cycle. SE induced apoptosis was accompanied by downregulation of Bcl-xL, upregulation of Bax, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase (PARP). Moreover, z-DEVD-fmk, a caspase-3 inhibitor, significantly inhibited cell cytotoxicity, apoptotic characteristics such as apoptotic bodies, sub-G(1) DNA content, and cleavage of PARP induced by SE. These results suggest that SE exerts its growth inhibitory effects on HL-60 cells through caspase-3-mediated induction of apoptosis. Therefore, SE offers promising chemotherapeuric potential to prevent cancers such as human leukemia.

Ieodomycins A-D, antimicrobial fatty acids from a marine Bacillus sp.

Bioassay-guided isolation of the EtOAc extract of a marine Bacillus sp., cultured in modified Bennetts broth medium, yielded four new antimicrobial fatty acids, named ieodomycins A-D. The planar structures of these new compounds were determined by extensive 1D and 2D NMR and HRESIMS spectroscopic data analysis. Their absolute configurations were elucidated by modified Moshers method and literature data review. All four new compounds demonstrated antimicrobial activities in vitro.

Gageotetrins A-C, noncytotoxic antimicrobial linear lipopeptides from a marine bacterium Bacillus subtilis.

Gageotetrins A-C (1-3), a unique class of linear lipopeptides, consisting of di- and tetrapeptides and a new fatty acid were isolated from a Marine Bacillus subtilis. The structures of 1-3 were assigned by spectroscopic data and their absolute stereochemistries were ascertained by chemical derivatization. Compounds 1-3 displayed good antimicrobial activities with MIC values of 0.01-0.06 μM. However, these compounds failed to register any cytotoxicity (GI50 > 30 μg/ml) against human cancer cell lines.

Cyclic Ether-Containing Macrolactins, Antimicrobial 24-Membered Isomeric Macrolactones from a Marine Bacillus sp.

Bioassay-guided isolation of bioactive metabolites from the ethyl acetate extract of a marine Bacillus sp. fermentation broth has led to the discovery of three new 24-membered macrolactones, macrolactins 1-3, which contain an oxetane, an epoxide, and a tetrahydropyran ring, respectively. The configurations of 1-3 were assigned by a combination of coupling constants, ROESY data analysis, and application of the modified Moshers method. Compounds 1-3 showed in vitro antimicrobial activity.

Macrolactin W, a new antibacterial macrolide from a marine Bacillus sp.

Bioactivity-guided isolation for the new/novel metabolites from the EtOAc extract obtained from the culture broth of a marine Bacillus sp. 09ID194 followed by chromatographic fractionations and subsequently HPLC purifications led to the isolation of two known macrolides, macrolactins A (1) and Q (2), together with a new glycosylated marcrolide, macrolactin W (3). The chemical structures of compounds 1-3 were assigned based on extensive MS and NMR spectral data analysis and literature review. Compound 3 showed potent antibacterial activity against both Gram-positive and Gram-negative pathogenic bacteria.

Synthetic analogs of indole-containing natural products as inhibitors of sortase A and isocitrate lyase.

Guided by the inhibitory activities of indole-containing natural products against isocitrate lyase (ICL) from Candida albicans and sortase A (SrtA) from Staphylococcus aureus, a series of compounds structurally analogous to natural products were synthesized. Eight SrtA inhibitors and an ICL inhibitor having higher activities than the natural products were discovered by screening the enzyme inhibitory activities of synthesized compounds. Among the SrtA inhibitors discovered, six exhibited higher activities than p-hydroxymercuribenzoic acid, which suggests that these compounds have great potential as alternative antibacterial agents.

Sesterterpenes from the tropical sponge Coscinoderma sp.

Eight new sesterterpenes (2, 5, and 10-15), including structurally related pentaprenyl hydroquinones (2 and 5), and seven known ones of the same structural classes were isolated from the sponge Coscinoderma sp., collected from Chuuk Island, Micronesia. On the basis of the results of combined spectroscopic analyses, the new compounds were determined to be derivatives of the halisulfates and suvanine. These compounds exhibited moderate cytotoxicity against the K562 cell line and inhibitory activities against isocitrate lyase, sortase A, and Na+/K+-ATPase; significant structure-activity relationships were evident.

Bromophenols as Candida albicans isocitrate lyase inhibitors.

A new series of bromophenols was synthesized by reactions of corresponding phenol analogs with bromine. The synthesized compounds were tested for inhibitory activity against isocitrate lyase (ICL) of Candida albicans and antimicrobial activity against gram-positive and, gram-negative bacteria and fungi. Among the synthesized bromophenols, bis(3-bromo-4,5-dihydroxyphenyl)methanone (11) and (3-bromo-4,5-dihydroxyphenyl)(2,3-dibromo-4,5-dihydroxyphenyl)methanone (12) displayed potent inhibitory activities against ICL, showing a stronger inhibitory effects than were found with natural bromophenol 1. The preliminary structure-activity relationships were investigated in order to determine the essential structural requirements for the inhibitory activities of these compounds against ICL of C. albicans.

Nortriterpene glycosides of the sarasinoside class from the sponge Lipastrotethya sp.

Five new nortriterpene glycosides, along with eight known compounds of the sarasinoside class, were isolated from the tropical sponge Lipastrotethya sp. collected from Chuuk, Micronesia. The structures of these new compounds, designated as sarasinosides N-R (9-13), were determined by combined spectroscopic and chemical methods. The aglycone portions of 10-13 were found to be unprecedented among nortriterpeneoids on the basis of extensive NMR analyses. Several of these compounds exhibited cytotoxicity against A549 and K562 cell lines as well as weak inhibitory activity against Na(+)/K(+)-ATPase.

Triterpene Galactosides of the Pouoside Class and Corresponding Aglycones from the Sponge Lipastrotethya sp.

Nine new triterpene galactosides and aglycones, along with three known compounds from the rare pouoside class, were isolated from the tropical sponge Lipastrotethya sp. collected from Micronesia. The structures of these new compounds were determined by combined spectroscopic methods and designated as pouosides F-I (4, 8, 10, and 12) and pouogenins A-E (5-7, 9, and 11). The absolute configurations of the asymmetric centers and the cyclohexenone moiety, which had been previously undetermined, were assigned by NOESY analyses and Moshers methods. Several of these compounds exhibited weak cytotoxicity against the K562 cell line.