Evaluation of the Acaricidal Activity of Coumarin Derivatives Obtained by Chemical Synthesis Against the Cattle Tick Rhipicephalus (Boophilus) Microplus

Introduction: Rhipicephalus (Boophilus) microplus is a parasitic tick that significantly impacts livestock production through economic losses and the transmission of diseases. Resistance to conventional acaricides, such as organophosphates, has prompted the search for alternative control strategies. Coumarin derivatives (Cds), due to their structural diversity and biological activity, have emerged as promising candidates for tick management. Methods: Twelve CDs were synthesized via Pechmann condensation under eco-friendly conditions and evaluated for acaricidal activity using the Adult Immersion Test (AIT) on engorged female ticks of the R. (B.) microplus Montecitos strain. Survival was monitored every 24 hours for 96 hours. Data were analyzed using Cox proportional hazards regression and Kaplan-Meier survival estimators to assess the effect of time, concentration, and compound type on tick mortality. Results: Survival decreased with increasing Cd concentration. Compounds C2 (5,7-dihydroxy-4-methylcoumarin), C4 (5-hydroxy-3,4,7-trimethyl-coumarin), and C11 (7-cinnamyloxy-4-methyl-coumarin) achieved the survival rates of ≤3% at 10 mg/ml within 96 hours, showing significantly greater efficacy than the organophosphate ethion, to which the Montecitos strain showed resistance (survival >98%). A hormetic response was observed in some treatments, with low concentrations inducing moderate tolerance. Discussion: The acaricidal activity of Cds was closely related to structural features, particularly substitutions at C-4 and C-7 positions. The multifunctional mechanisms of coumarins, including interference with calcium signaling and detoxification pathways, may reduce resistance development. The ineffectiveness of ethion reinforces the need for novel control strategies. Ethanol as a solvent did not affect tick survival, confirming the bioactivity was due to the Cds themselves. Conclusion: Coumarin derivatives synthesized under sustainable conditions demonstrate strong acaricidal potential, especially C2, C4, and C11. These compounds could serve as eco-friendly alternatives to conventional acaricides in controlling R. (B.) microplus, particularly in populations resistant to conventional treatments. Furthermore, in vivo and environmental impact studies are recommended to validate their practical application.