Cytotoxic and Insecticidal Activities of Derivatives of Harmine, a Natural Insecticidal Component Isolated from Peganum harmala

Yong Zeng,Guohua Zhong,Yaomou Zhang,Qunfang Weng,Meiying Hu

doi:10.3390/molecules15117775

Yong Zeng, Guohua Zhong + Show 3 more

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https://doi.org/10.3390/molecules15117775

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Abstract

In a continuing effort to develop novel β-carbolines endowed with better insecticidal activity, a simple high-yielding method for the synthesis of harmine compounds starting from L-tryptophan has been developed and a series of 1,3-substituted β-carboline derivatives have been synthesized and evaluated for their cytotoxicity against insect cultured Sf9 cell line in vitro and insecticidal activities against 4th instar larvae of mosquitos, Culex pipiens quinquefasciatus and mustard aphid, Lipaphis erysimi. The results demonstrated that 1-phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (compound 2) and methyl 1-phenyl-β-carboline-3-carboxylate (compound 13) represented the best potential compounds, with Sf9 cells inhibition rates of 71.55% and 60.21% after 24 h treatment at concentrations of 50–200 mg/L, respectively. Both compounds 2 and 13 also showed strong insecticidal activity towards 4th instar larvae of mosquitos with LC50 values of 20.82 mg/L and 23.98 mg/L, and their LC90 values were 88.29 mg/L and 295.13 mg/L, respectively. Furthermore, the LC50 values of compounds 2 and 13 against mustard aphids were 53.16 mg/L and 68.05 mg/L, and their LC90 values were 240.10 mg/L and 418.63 mg/L after 48 h treatment. The in vitro cytotoxicity of these compounds was consistent with the insecticidal activity in vivo. The results indicated that the 1- and 3-positions of the β-carboline ring deserve further investigation to develop biorational insecticides based on the natural compound harmine as a lead compound.

Highlights

Harmine compounds and structurally related compounds, belonging to the β-carboline alkaloids, and found in medicinal plants such as Peganum harmala and Eurycoma longifolia, have recently drawn increasing interest due to their diverse pharmacological, neurophysiologic and biochemical activities [1,2,3,4,5,6]
This paper describes work aimed at preparing a series of new carboline derivatives that might possesses cytotoxic and insecticidal activity
Five tetrahydro-β-carboline carboxylic acids 1-5 were produced by Pictet–Spengler reaction of L-tryptophan with five different aldehydes (Table 1)

Summary

Introduction

Harmine compounds and structurally related compounds, belonging to the β-carboline alkaloids, and found in medicinal plants such as Peganum harmala and Eurycoma longifolia, have recently drawn increasing interest due to their diverse pharmacological, neurophysiologic and biochemical activities [1,2,3,4,5,6]. As for pest management Peganum L. plant species extracts, whose main components include a mixture of harmine, harmaline, norharman and their derivatives, have been long known to have insecticidal, fungicidal and plant growth regulatory properties [9,10,11,12,13,14,15]. When incorporated into the diet, harmaline caused larval weight loss with a reduction in protein and glycogen contents and an inhibition of α-amylase activity. Another study revealed an elevated juvenile hormone epoxide hydrolase (JHEH)

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