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Investigation of novel pyrazole carboxamides as new apoptosis inducers on neuronal cells in Helicoverpa zea.

Abstract：

:Novel pyrazole carboxamides with a diarylamine-modified scaffold were modified based on the bixafen (Bayer) fungicide, which has excellent activity against Rhizoctonia solani, Rhizoctonia cerealis and Sclerotinia sclerotiorum. To discover the potential insecticidal activity of these novel pyrazole carboxamides, the present study explored their possible cytoactivity on the insect neuronal cells (RP-HzVNC-AW1) in Helicoverpa zea. The preliminary bioassays showed that some of the target compounds exhibited good cytoactivity against AW1 cells. Among them, compounds a5 and b4-b7 showed good activity in vitro with IC50 values of 11.28, 10.46, 9.04, 11.72 and 12.19 μM, respectively. Notably, the IC50 value of compound b5 was better than 11.81 μM for fipronil. We subsequently attempted to illustrate the mechanism of b5. Intracellular biochemical assays showed that b5 induced AW1 cell apoptosis with a decrease in themitochondrial membrane potential, as well as a significantly increased intracellular calcium ion concentration and caspase-3 activity. A significant decrease in Bcl-2 levels and a marked augmentation of cytochrome-c and Bax were also detected. These results indicate that a mitochondrially dependent intrinsic pathway contributes to compound b5-induced apoptosis in AW1 cells. This study suggests that b5 may act as a potential insecticide that can be used for further optimization.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Ren Y,Yang N,Yue Y,Jin H,Tao K,Hou T

doi

10.1016/j.bmc.2018.03.010

subject

Has Abstract

pub_date

2018-05-15 00:00:00

pages

2280-2286

issue

9

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(17)32421-5

journal_volume

26

pub_type

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