Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 67, Issue 45, Pages 12538-12546Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.9b02878
Keywords
synthesis; PDHc-E1 inhibitor; anticyanobacteria; selectivity; molecular docking
Funding
- National Research and Development Plan [2017YFD0200506]
- National Natural Science Foundation of China [21877047, 31701820, 21472062, 21907035]
- 111 Project [B17019]
- Natural Science Foundation of Hubei Province of China [2017CFB232]
- National Key Research Development Program of China [2018YFD0200100]
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Cyanobacteria harmful algal blooms are of global concern, but all currently available algicides in the market are nonselective and have potential side effects on nontarget species. In the present work, two series of compounds (4 and 6) comprising 16 novel 1,2,3-triazole aminopyrimidines were rationally designed and synthesized as control agent for cyanobacteria. Our design focus was the inhibiting cyanobacteria by inhibition against pyruvate dehydrogenase complex E1 (PDHc-E1). Compounds 4 and 6 showed potent inhibition against Escherichia coli PDHc-E1 (IC50 = 4.13-23.76 mu M) and also strong algicidal activities against Synechocystis sp. PCC 6803 (EC50 = 1.7-8.1 mu M) and Microcystis sp. FACHB905 (EC50 = 2.1-11.8 mu M). In particular, the algicidal activities of 6d against four algal species were not only higher than that of prometryn; they were also comparable to or higher than that of copper sulfate. The analogues 4c, 4d, 6d, and 6e displayed potent algicidal activities and inhibition of E. coli PDHc-E1 but exhibited negligible inhibition of porcine PDHc-E1. As revealed by molecular docking, site-directed mutagenesis, enzymatic assays, and an inhibition kinetic analysis, 4c and 6d inhibited PDHc-E1 in a competitive manner.
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