Bioactivities of algicidal C18 hydroxy unsaturated fatty acid isolated from the red alga Tricleocarpa jejuensis and its synthesized propargylic derivative

(±)-(E)-12-hydroxyoctadec-10-enoic acid (compound A) was isolated from the red alga Tricleocarpa jejuensis in our previous study as a potent algicidal compound against red tide microalga Chattonella antiqua (Ochrophyta, Raphidophyceae). Interestingly, its propargylic derivative, 12-hydroxyoctadec-10-ynoic acid (compound B), which was obtained as a synthetic intermediate of compound A, showed an even more extensive algicidal activity. In this study, the effects of compound A and B on the major causative species of harmful algal blooms (HABs) such as Chattonella marina (Ochrophyta, Raphidophyceae), Heterocapsa circularisquama, and Karenia mikimotoi (Miozoa, Dinophyceae) in addition to C. antiqua were investigated. Both compounds exhibited toxic effects on these red tide flagellates in a concentration dependent manner with LC50 < 10 μg/mL, and the activities of compound B were much stronger than compound A. Zooplankton rotifer (Brachionys plicatilis) was relatively resistant to the compounds, and the lethal effects of H. circularisquama and K. mikimotoi on rotifers were reduced in the presence of compound A and B, suggesting their potential usage in the mitigation strategy for HABs. Consistent with the toxicities on the HAB species, compound B showed stronger cytotoxicity on HeLa, XC, and U937 cells than A. Since compound B but not compound A showed haemolytic activity on rabbit erythrocytes, specific action of compound B on cell membrane may be responsible for the potent cytotoxicity. Furthermore, compound B exhibited higher antibacterial effect on Staphylococcus aureus than compound A, while both were not effective on Enchiridia coli. Our results suggest that compound A and B are promising multifunctional candidates with potential to develop not only as anti-red tide microalgae but also as tumor cell-killing and antibacterial agents. This is the first report indicating that replacing a double bond in the hydroxy unsaturated fatty acid with a triple bond results in much augmentation of the bioactivities

Algicidal hydroxylated C18 unsaturated fatty acids from the red alga Tricleocarpa jejuensis: Identification, synthesis and biological activity

Bioassay-guided separation of a methanol extract of Tricleocarpa jejuensis by monitoring algicidal activity against the red tide phytoplankton Chattonella antiqua led to the isolation of an active fraction consisting of a mixture of four isomeric compounds. The active compounds were identified as (E)-9-hydroxyoctadec-10-enoic acid (1), (E)-10-hydroxyoctadec-8-enoic acid (2), (E)-11-hydroxyoctadec-12-enoic acid (3) and (E)-12-hydroxyoctadec-10-enoic acid (4) by NMR, IR and mass spectral data. The structures were confirmed by comparison of the NMR and MS data with those of authentic samples of 1?4 obtained by unambiguous syntheses. Synthesized hydroxy acids 1?4 and related compounds were assessed for algicidal activity against C. antiqua and it was found that all of 1?4 had high activity (>80% mortality at 24 h) at a concentration of 20 μg/mL. A structure?activity relationship study using 11 related compounds revealed that the presence of the hydroxyl group is important for the activity and the double bond may be replaced with a triple bond

Induction of Apoptotic Cell Death in Human Leukemia U937 Cells by C18 Hydroxy Unsaturated Fatty Acid Isolated from Red Alga <i>Tricleocarpa jejuensis</i>

Our previous studies have found that (±)-(E)-12-hydroxyoctadec-10-enoic acid (HOEA) isolated from the red alga Tricleocarpa jejuensis showed cytotoxic effects on various living organisms including harmful microalgae, Gram-positive bacteria, and mammalian tumor cells. Since natural products with apoptosis-inducing ability can be promising anti-cancer agents, in this study, we investigated the cytotoxic mechanism of HOEA on U937 cells focusing on apoptosis induction. HOEA showed much stronger cytotoxic and cytolytic effects on U937 cells than elaidic acid, which has similar structure but no 12-hydroxy group, suggesting that hydroxy group is important for the cytotoxicity of HOEA. HOEA induced apoptotic nuclear morphological changes, DNA fragmentation, and decrease in mitochondrial membrane potential. Furthermore, time-dependent increase in annexin V+/PI+ cell population in HOEA-treated U937 cells was detected. Among the apoptosis-related reagents, caspase-family inhibitor almost completely inhibited HOEA-induced DNA fragmentation. In the analyses using specific caspase-substrates, extremely high cleavage activity toward caspase-3/7/8 substrate was observed in HOEA-treated U937 cells, and weak activities of caspase-1 and -3 were detected. Analyses using specific caspase inhibitors suggested that caspase-3 and caspase-8 might be predominantly responsible for the cleavage activity. Activation of these caspases were also confirmed by western blotting in which significant levels of cleaved forms of caspase 3, caspase 8, and PARP were detected in HOEA-treated U937 cells. Our results suggest that HOEA is capable of inducing apoptosis in U937 cells in which caspase-3 and caspase-8 might play important roles. Since the cytotoxic effect of HOEA is not strictly specific to tumor cells, development of appropriate drug delivery system for selective tumor targeting is necessary for the clinical applications to reduce the possible side effects

Synthesis and structure-activity relationship study of aldose reductase inhibiting marine alkaloid lukianol A and its derivatives

Lukianol A (1a) and its six derivatives 1b-1g, in which each hydroxyl groups of 1a was individually modified, were synthesized via the common intermediate 7a, which was obtained by condensation of the styryl carbazate 10 with p-hydroxyphenylpyruvic acid and subsequent [3,3]-sigmatropic rearrangement. The synthesized lukianol derivatives were evaluated for their ability to inhibit human aldose reductase. 4′-O-methyl (1b) and 4′-dehydroxy (1g) derivatives showed the same level of inhibitory activity as 1a (IC50 2.2 µM), indicating that the 4′-OH is irrelevant for the activity. In contrast, methylation of the hydroxyl group at the 4″′-position (1d) resulted in the loss of activity at a concentration of 10 µM, and masking the hydroxyl group at the 4″-position (1e) caused a 9-fold decrease in activity compared with that of 1b, suggesting that the 4″-OH is an essential group, and the 4″′-OH is required for higher activity

Coexistence and Adsorption Properties of Heavy Metals by Polypropylene Microplastics

Plastic particles with a diameter of 5 mm or less are called microplastics. Microplastics are one of the primary sources of pollution in the environment. It has been proven that microplastics are also carriers of heavy metals, but there are few studies on their adsorption mechanism. In this study, the adsorption of Pb, Cu, Cd, and Zn by polypropylene (PP) microplastics was analyzed and discussed. The morphology of PP was observed by scanning electron microscopy (SEM), the surface elemental composition of PP was determined by X-ray photoelectron spectroscopy (XPS), and the functional groups of PP were analyzed by Fourier transform infrared spectroscopy (FTIR). The results showed that the adsorption behavior of microplastics to different heavy metals could be balanced in 32 hours. Kinetics experiments showed that the adsorption process could be fitted well by a two-stage dynamic model, and the adsorption of Pb and Cu by PP is greater than that of Cd and Zn. The Freundlich model has the best fitting effect on Pb for the adsorption isothermal results. The Langmuir model showed that the process is favorable for adsorption. The adsorption of mixed heavy metals by microplastics showed that when the concentration of the mixed adsorption mass was low, the presence of a coexistence system promoted the adsorption of Zn and Cu by microplastics. With an increasing concentration, the adsorption of 4 heavy metals by microplastics is inhibited