# Acaricidal activity of small molecule antagonists of the tick kinin receptor against Rhipicephalus microplus acaricide‐susceptible and resistant strains

## TL;DR

Researchers tested small molecules that target a tick receptor and found they effectively kill both susceptible and resistant tick strains, with one also reducing tick reproduction.

## Contribution

Two small molecules were identified as effective against acaricide-resistant ticks and one reduced tick reproduction.

## Key findings

- SACC-0039590 and SACC-0428788 killed larvae of both susceptible and resistant R. microplus strains.
- SACC-0039590 reduced egg mass weight and hatching in female ticks.
- The compounds showed low toxicity when tested with adjuvant combinations.

## Abstract

Resistance to acaricides underscores the need for tick control alternatives. We previously identified in a high‐throughput screen six small molecules SACC‐0412060, SACC‐0412062, SACC‐0412066, SACC‐0064443, SACC‐0428788, and SACC‐0039590 as antagonists of the kinin receptor from Rhipicephalus microplus. The acaricidal activity of these molecules was investigated.

The toxicities of adjuvant/solvent combinations of a rapeseed oil methyl ester or a propylene carbonate in 5% DMSO versus 5% DMSO alone were evaluated using a larval immersion test (LIT) with the R. microplus susceptible Deutch strain, and all were non‐toxic. The rapeseed oil methyl ester (1%) in 5% DMSO was adopted as the adjuvant for all molecules in bioassays. Permethrin (3.19 mM) killed all larvae. The Deutch strain mortality with SACC‐0039590 and SACC‐0428788 (both at 1 mM) was 100% and 73.65%, respectively, while ranged from 2.7% to 3.8% with the other small molecules. In the LIT, the LC50 of SACC‐0039590 and SACC‐0428788 were 60 μM, and 450 μM, respectively. For the R. microplus Arauquita pyrethroid‐resistant strain in the LIT, the LC50 of SACC‐0039590 and SACC‐0428788 were 60 μM and 237.5 μM respectively. SACC‐0039590 (N‐[2‐(4‐chlorophenyl)ethyl]‐5‐methylthieno[2,3‐d]pyrimidin‐4‐amine) and SACC‐0428788 (N‐[2‐(4‐chlorophenyl)ethyl]thieno[2,3‐d]pyrimidin‐4‐amine) are structural analogs, the first one featuring a 5‐methyl group absent in the second. For engorged Deutch females, immersion in SACC‐0039590 caused dose‐dependent reductions in egg mass weight (~35%) and egg hatching (21%–38.59%). Permethrin (3.19 mM) significantly reduced egg mass weight but not egg hatching.

The small molecule SACC‐0039590 killed susceptible and pyrethroid‐resistant larvae of R. microplus and reduced the reproductive output of females. © 2025 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Two small molecules, SACC‐0039590 and SACC‐0428788, killed cattle fever tick, R. microplus, susceptible Deutch strain and pyrethroid resistant Arauquita strain larvae. SACC‐0039590 at 1 mM decreased the reproductive parameters of Deutch females.