Design, Synthesis, and Insecticidal Activity of 5,5-Disubstituted 4,5-Dihydropyrazolo[1,5-a]quinazolines as Novel Antagonists of GABA Receptors

Abstract

To control the development of resistance to conventional insecticides acting as γ-aminobutyric acid (GABA) receptor antagonists (e.g., fipronil), new GABAergic 5,5-disubstituted 4,5-dihydropyrazolo­[1,5-a]­quinazolines were designed via a scaffold-hopping strategy and synthesized with a facile method. Among the 50 target compounds obtained, compounds 5a, 5b, 7a, and 7g showed excellent insecticidal activities against a susceptible strain of Plutella xylostella (LC50 values ranging from 1.03 to 1.44 μg/mL), which were superior to that of fipronil (LC50 = 3.02 μg/mL). Remarkably, the insecticidal activity of compound 5a was 64-fold better than that of fipronil against the field population of fipronil-resistant P. xylostella. Electrophysiological studies against the housefly GABA receptor heterologously expressed in Xenopus oocytes indicated that compound 5a could act as a potent GABA receptor antagonist, and IC50 was calculated to be 32.5 nM. Molecular docking showed that the binding poses of compound 5a with the housefly GABA receptor can be different compared to fipronil, which explains the effectiveness of compound 5a against fipronil-resistant insects. These findings have suggested compound 5a as a lead compound for a novel GABA receptor antagonist controlling field-resistant insects and provided a basis for further design, structural modification, and development of 4,5-dihydropyrazolo­[1,5-a]­quinazoline motifs as new insecticidal GABA receptor antagonists.

Design, synthesis, insecticidal activities, and molecular docking of novel pyridylpyrazolo carboxylate derivatives

“…Insecticidal activities of synthesized compounds and positive control (chlorantraniliprole, 98% purity) against P. xylostella (third-instar larvae) were tested indoors according to the literatures [23,24]. Each of the test compounds was dissolved in DMSO and diluted with distilled water containing Tween 80 (0.1%, v/v) to obtain desired concentrations.…”

Advances in Control Strategies against Spodoptera frugiperda. A Review

“…Its effectiveness was 2–4 times better in field tests than the commercially available standards. In the search for new insecticides, 4,5-dihydropyrazolo [1,5- a ] quinazoline derivatives have also been included as GABA receptor antagonist inhibitors, resulting in a mortality of up to 79.63% [ 29 ].…”

“…Its effectiveness was 2-4 times better in field tests than the commercially available standards. In the search for new insecticides, 4,5-dihydropyrazolo [1,5-a] quinazoline derivatives have also been included as GABA receptor antagonist inhibitors, resulting in a mortality of up to 79.63% [29]. Derivatives of 7-chloro-4-(1H-1,2,3-triazol-1-yl) quinoline (Figure 6) have been evaluated on the fourth instar of S. frugiperda to explore their insecticidal and antifeedant activity and acetylcholinesterase inhibition.…”

“…Its effectiveness was 2-4 times better in field tests than the commercially available standards. In the search for new insecticides, 4,5-dihydropyrazolo [1,5-a] quinazoline derivatives have also been included as GABA receptor antagonist inhibitors, resulting in a mortality of up to 79.63% [29]. and diethylcarbamodithioate to improve their activity through chemical synthesis, enhancing this activity at low concentrations; the structures of these new matrine derivatives are shown in Figure 4 [1].…”

4‐Oxo‐4,5,6,7‐tetrahydro‐1H‐pyrazolo[3,4‐d]pyrimidine Derivatives: Design, Synthesis, Insecticidal Assay and Binding Mode Studies

“…[18] 4,5-dihydropyrazolo [1,5-a] quinazoline derivatives (compounds 2 and 3, Figure 1) were reported by Xu. [19,20] The 48 h LC 50 value against Plutella xylostella of compound 2 (3.87 mg/L) was near to that of fipronil (1.80 mg/L). [19] The 24 h activity against Plutella xylostella of compound 3 was superior to that of fipronil with the LC 50 values 1.17 mg/L and 3.02 mg/L, respectively.…”