Nontoxic piperamides and their synthetic analogues as novel antifouling reagents

Abstract

Bioassay-guided isolation of an acetone extract from a terrestrial plant Piper betle produced four known piperamides with potent antifouling (AF) activities, as evidenced by inhibition of settlement of barnacle cypris larvae. The AF activities of the four piperamides and 15 synthesized analogues were compared and their structure–activity relationships were probed. Among the compounds, piperoleine B and 1-[1-oxo-7-(3′,4′-methylenedioxyphenyl)-6E-heptenyl]-piperidine (MPHP) showed strong activity against settlement of cyprids of the barnacle Balanus amphitrite, having EC₅₀ values of 1.1 ± 0.3 and 0.5 ± 0.2 μg ml⁻¹, respectively. No toxicity against zebra fish was observed following incubation with these two compounds. Besides being non-toxic, 91% of piperoleine B-treated cyprids and 84% of MPHP-treated cyprids at a concentration of 100 μM completed normal metamorphosis in recovery bioassays, indicating that the anti-settlement effect of these two compounds was reversible. Hydrolysis and photolysis experiments indicated that MPHP could be decomposed in the marine environment. It is concluded that piperamides are promising compounds for use in marine AF coatings.

Keywords:

• Piper betle
• piperamides
• antifouling compounds
• activity relationship
• hydrolysis and photolysis

Acknowledgements

This study was supported by a grant (DY125-15-T02) from the China Ocean Mineral Resources Research and Development Association, an award (SA-C0040/UK-C0016) from the King Abdullah University of Science and Technology to Pei-Yuan Qian and the National Natural Science Foundation of China (No. 21262047). The authors are grateful to the School of Chemistry and Biotechnology, Yunnan University of Nationalities for measuring the NMR and MS spectra. They also acknowledge Dr Zilong Wen of the Hong Kong University of Science and Technology for providing zebra fish embryos.