A novel thiazolidinedione derivative TD118 showing selective algicidal effects for red tide control.

Thiazolidinedione (TD) derivatives have been found to have an algicidal effect on harmful algal bloom microalgae. In this study, 75 TD derivatives were synthesized and analyzed for algicidal activity. Among these synthetic TDs, 18 TD derivatives showed specific algicidal activity on two strains belonging to the classes Raphidophyceae (Chattonella marina and Heterosigma akashiwo) and Dinophyceae (Cochlodinium polykrikoides). Two strains belonging to Bacillariophyceae (Navicula pelliculosa and Phaeodactylum EPV), one strain belonging to Dinophyceae (Amphidinium sp.), and a Eustigmatophycean microalga (Nannochloropsis oculata) showed less sensitivity to the TD derivatives than the other two phyla. The most reactive TD derivative, compound 2 (TD118), was selected and tested for morphological and physiological changes. TD118 effectively damaged the cell membrane of C. marina, H. akashiwo and C. polykrikoides. The O2 evolution and photosystem II efficiency (F(v)/F(m)) of C. marina, H. akashiwo and C. polykrikoides were also severely reduced by TD118 treatment. Amphidinium sp., N. pelliculosa, Phaeodactylum EPV and N. oculata showed less reduction of O2 evolution and the F(v)/F(m) by TD118. These results imply that the species-specific TD structure relationship may be due to structural and/or physiological differences among microalgal species.

Algicidal activity of thiazolidinedione derivatives against harmful algal blooming species.

Thiazolidinedione (TD) derivatives exhibit algicidal activity against harmful algal blooming species such as Chattonella marina, Heterosigma akashiwo, and Cochlodinium polykrikoides, as reported previously. In this study, the efficacies and selectivities of TD derivatives were tested by analyzing the structure-activity relationships of various TD derivatives. To investigate structure-activity relationships for growth inhibition of harmful algae, we added a methylene group between the cyclohexyl ring and oxygen of 5-(3-chloro-4-hydroxybenzylidene)-TD, which decreased the inhibitory potency of compound 17. Interestingly, another addition of a methylene group significantly increased the inhibitory potency against C. polykrikoides. The addition of 1 µM compound 17 resulted in the cell rupture of harmful algae after less than 10 h incubation at 20 °C. Compound 17 was applied to both harmful and non-harmful algae and showed a drastic reduction in the efficiency of photosystem II, resulting in reduced photosynthetic oxygen evolution. Compound 17 at a 5 µM concentration destroyed all of the harmful algae, while algicidal activity against non-harmful algae did not exceed 30% of the control within the concentration range tested. In contrast, a herbicide, 3-(3,4-dichlorophenyl)-1,1-dimethylurea, tested at a 5 µM concentration, exhibited 40-70% algicidal activity relative to that of the control against both harmful and non-harmful algae. Compound 17 is a promising lead compound for the development of algicides to control harmful algal blooming species.

Enhanced efficacy of TD53, a novel algicidal agent, against the harmful algae via the liposomal delivery system.

The present study aimed to design the liposomal delivery system for TD53, a novel algicial drug in order to improve the delivery properties of TD53 and evaluate its algicidal effects as well as selectivity against harmful and non-harmful algae. Liposomes of TD53 were prepared with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) by a lyophilization, resulting in relatively small size vesicles (234±38nm) and narrow size distribution (PI=0.130±0.027). The drug leakage from the liposome was negligible in the F/2 media (<2% during 96h incubation). Subsequently algicidal activity of liposomal TD53 against harmful and nonharmful algae was evaluated at various concentrations. The IC(50) values of TD53 in liposome against harmful algae such as Chattonella marina, Heterosigma akashiwo and Cocholodinium polykrikoides were 2.675, 2.029, and 0.480µM, respectively, and were reduced by approximately 50% compared to those obtained from non-liposomal TD53. In contrast, the algicidal effect of liposomal TD53 was insignificant against non-harmful algae including Navicula pelliculosa, Nannochloropsis oculata and Phaeodactylum EPV. Those results suggested that liposomal delivery systems might be effective to enhance the efficacy of TD53 while maintaining the selectivity to harmful algal species.