Tyrosinase-mediated synthesis of larvicidal active 1,5-diphenyl pent-4-en-1-one derivatives against Culex quinquefasciatus and investigation of their ichthyotoxicity

Sathishkumar Chidambaram,Daoud Ali,Saud Alarifi,Raman Gurusamy,Idhayadhulla Akbar,Surendrakumar Radhakrishnan

doi:10.1038/s41598-021-98281-5

Sathishkumar Chidambaram, Daoud Ali + Show 4 more

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https://doi.org/10.1038/s41598-021-98281-5

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Abstract

1,5-diphenylpent-4-en-1-one derivatives were synthesised using the grindstone method with Cu(II)-tyrosinase used as a catalyst. This method showed a high yield under mild reaction conditions. The synthesised compounds were identified by FTIR, 1H NMR, 13C NMR, mass spectrometry, and elemental analysis. In this study, a total of 17 compounds (1a–1q) were synthesised, and their larvicidal and antifeedant activities were evaluated. Compound 1i (1-(5-oxo-1,5-diphenylpent-1-en-3-yl)-3-(3-phenylallylidene)thiourea) was notably more active (LD50: 28.5 µM) against Culex quinquefasciatus than permethrin(54.6 µM) and temephos(37.9 µM), whereas compound 1i at 100 µM caused 0% mortality in Oreochromis mossambicus within 24 h in an antifeedant screening, with ichthyotoxicity determined as the death ratio (%) at 24 h. Compounds 1a, 1e, 1f, 1j, and 1k were found to be highly toxic, whereas 1i was not toxic in antifeedant screening. Compound 1i was found to possess a high larvicidal activity against C. quinquefasciatus and was non-toxic to non-target aquatic species. Molecular docking studies also supported the finding that 1i is a potent larvicide with higher binding energy than the control (− 10.0 vs. − 7.6 kcal/mol) in the 3OGN protein. Lead molecules are important for their larvicidal properties and application as insecticides.

Highlights

1,5-diphenylpent-4-en-1-one derivatives were synthesised using the grindstone method with Cu(II)tyrosinase used as a catalyst
We identified the most effective and prepared active larvicidal Mannich base synthesis derivatives using the grindstone method using Cu(II)-tyrosinase as a catalyst, which is economical and leads to good coating and high yield
These compounds were investigated for their use as larvicides against Culex quinquefasciatus and for their toxicity against non-target aquatic species through ichthyotoxic activity

Summary

Introduction

1,5-diphenylpent-4-en-1-one derivatives were synthesised using the grindstone method with Cu(II)tyrosinase used as a catalyst. This method showed a high yield under mild reaction conditions. A total of 17 compounds (1a–1q) were synthesised, and their larvicidal and antifeedant activities were evaluated. The active core of the deoxy type [Cu(I)–Cu(I)] contains two cuprous ions, which attach dioxygen to produce the oxy form. The met type of tyrosinase is an enzymatic form wherein two cupric ions are bridged by one or two tiny ligands, along with water molecules or hydroxide ions, while the enzyme is at rest and acting as a catalyst. The present study focused on the grindstone green chemistry method in order to overcome the abovementioned challenges in the preparation of Mannich base derivatives

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