Synthesis and Photoactivated Toxicity of 2-Thiophenylfuranocoumarin Induce Midgut Damage and Apoptosis in Aedes aegypti Larvae

Abstract

Furanocoumarins are photoactive compounds derived from secondary plant metabolites. They possess many bioactivities, including antioxidative, anticancer, insecticidal, and bactericidal activities. Here, we designed a new scheme for synthesizing 2-arylfuranocoumarin derivatives by condensation, esterification, bromination, and Wittig reaction. We found that 2-thiophenylfuranocoumarin (Iy) had excellent photosensitive activity. Three Iy concentrations (LC25, LC50, and LC75) were used to treat the fourth instar larvae of Aedes aegypti (A. aegypti). The photoactivated toxicity, sublethal dose, mitochondrial dysfunction, oxidative stress level, intestinal barrier dysfunction, and apoptosis were studied. The results showed that Iy induced reactive oxygen species (ROS) production in midgut cells under ultraviolet light. Ultrastructural analysis demonstrated that mitochondria were damaged, and the activities of related enzymes were inhibited. Ultimately, Iy exposure led to excessive ROS production followed by the inhibition of antioxidant enzymes, including SOD, CAT, GPx, and GR, which diminished ROS elimination and escalated oxidative stress in midgut cells, aggravating the degree of oxidative damage in these cells. Histopathological changes were observed in the midgut, which led to intestinal barrier dysfunction. When the elimination of ROS was blocked and it accumulated in cells, apoptosis-related genes, including AeDronc, AeCaspase7, and AeCaspase8, were induced and activated. In addition, Iy affected the growth and development of A. aegypti at sublethal concentrations, and there was an obvious post-lethal effect. Thus, we found that Iy caused midgut damage and apoptosis in A. aegypti larvae under ultraviolet light, which preliminarily revealed the mode of action of Iy in A. aegypti.

Potential Biochemical Pesticide—Synthesis of Neofuranocoumarin and Inhibition the Proliferation of Spodoptera frugiperda Cells through Activating the Mitochondrial Pathway

“…However, natural furanocoumarin compounds have poor biological activity against pests, therefore, based on the structure of furanocoumarin, the authors designed and synthesized a series of 2-substituted furanocoumarin derivatives to increase the π-conjugated system in the furanocoumarin structure. In the early stage of our laboratory work, it was also confirmed that 2-thiophenefurocoumarin had excellent photosensitivity to the fourth instar larvae of Aedes aegypti and induced midgut tissue apoptosis [ 17 ]. In this study, 39 compounds were obtained ( Text S1, Figure S1 ).…”

“…The synthesis of the compounds in the manuscript refers to the previous research of the College of Plant Protection, Hainan University [ 17 , 39 ].…”

Discovery of Pesticide Candidates from Natural Plant Products: Semisynthesis and Characterization of Andrographolide-Based Esters and Study of Their Pesticidal Properties and Toxicology

“…Normally in insects, the SOD enzyme scavenges O 2– to H 2 O 2 , which is then converted to H 2 O by CAT and POD enzymes . As depicted in Figure and Tables S3–S5 (see the Supporting Information), the changes of CAT, POD, and SOD enzyme activities of S.…”

Antidiabetic Function of Lactobacillus fermentum MF423-Fermented Rice Bran and Its Effect on Gut Microbiota Structure in Type 2 Diabetic Mice

“…The development of insulin resistance affects oxidative stress in diabetic mice, leading to a significant increase in the levels of reactive oxygen species (ROS) and MDA in mice ( Li et al, 2021 ). Previous studies have proven that a large number of antioxidant enzymes in organisms, such as SOD, T-AOC and GSH-PX, can suppress oxidative stress by scavenging ROS levels ( Liu S. W. et al, 2020 ; Wu et al, 2021 ). The liver is the largest metabolic organ possessing abundant antioxidant enzymes.…”