Phenotypic and Target-Directed Screening Yields New Acaricidal Alternatives for the Control of Ticks

Area of Science:

• Veterinary Entomology
• Chemical Ecology
• Drug Discovery

Background:

• Rhipicephalus microplus (common cattle tick) causes significant global economic losses in livestock.
• Tick-borne diseases transmitted by R. microplus pose a major health concern.
• Widespread acaricide resistance in R. microplus necessitates the development of novel control strategies.

Purpose of the Study:

• To identify new compounds for controlling acaricide-resistant Rhipicephalus microplus.
• To explore natural extracts from Mexican traditional medicine and synthetic organic molecules.
• To evaluate compounds for their efficacy and selectivity against ticks and their potential toxicological profile.

Main Methods:

• Phenotypic screening of 44 natural extracts and 33 synthetic compounds using BME26 embryonic cells.
• Target-directed screening for inhibitors of tick triosephosphate isomerase.
• In vitro assays against adult and larval Rhipicephalus microplus, and cytotoxicity tests on mammalian cells.

Main Results:

• Ten natural extracts and 13 synthetic compounds inhibited tick cell growth.
• A potent and selective inhibitor of tick triosephosphate isomerase was identified.
• Two compounds demonstrated potent in vitro acaricidal activity against adult and larval ticks, with good selectivity over mammalian cells.

Conclusions:

• Novel compounds derived from natural sources and synthetic chemistry show significant potential for Rhipicephalus microplus control.
• The identified compounds offer a promising alternative to existing acaricides due to their efficacy and favorable toxicological profiles.
• Further development of these compounds could lead to effective strategies against resistant cattle tick populations.