Structure-Repellence Potential of Stereoisomers of Menthane-Diol and Analogues against the Brown Ear tick (Rhipicephalus appendiculatus)

Abstract

Tick-borne infections in livestock are wide-spread in Africa. They present a great constraint to livestock development, particularly in the improvement of local breeds. This is due to the fact that many different tick-borne infections occur in the continent. This prob lem is magnified by the high susceptibility of foreign breeds of livestock being used to improve livestock productivity in many African countries. Brown Ear tick, Rhipicephalus appendiculatus, is the vector of Theileria parva, the pathogen of the tick–borne disease, East Coast Fever. A commonly used conventional arthropod repellent N, N-diethyl-3-methylbenzamide (DEET) is still used for repelling a wide range of insects such as, ticks and mites by many famers in Kenya. However, conventional drugs have many harmful effects to both the animals and human beings, additionally they cause considerable environmental pollution. In search for effective green and non-toxic alternatives to DEET against different hematophagous arthropods, there has been renewed interest in repellents of botanical origin. Phytochemicals have arguably fewer side effects and are readily available. A monoterpene of relatively low volatil ity, p-menthane-3,8-diol (PMD), obtained from lemon eucalyptus leaves (Eucalyptus citriodora) has shown potent repellence against mosquitoes. This study was designed to evaluate the structure-activity studies of p-menthane-3,8-diol stereoisomers and analogues against the Brown ear tick. The essential oil of lemon eucalyptus was extracted by hydrodistillation. Commercial standards of (+) and (-)-isopulegol were hydrated at C-8 using the oxy-mercuration/demercuration procedure to obtain (+) and (–)-trans-p-men thane-3,8-diol respectively. (±)-Cis-p-menthane-3,8-diol stereoisomers were prepared from (±)-citronellal via the Zimmermann and English procedure that involved acid catalyzed cyclization of (±)-citronellal. GC-MS was used to identify the chemical composition of E. citriodora oil, while the structural elucidation of the synthesized PMD stereoisomers was done using 1H-NMR and 13C-NMR spectroscopy. The E. citriodora oil, menthane diol stereoisomers, its analogues and DEET were screened for their repellent activity against R. appendiculatus, through subjecting them to a dual choice tick climbing bioassay. The results revealed that methane diols were potently repellent against R. appendiculatus and comparable to that of DEET. Racemates of cis and trans were as repellent as (+) and (−)-trans diols. PMD analogues of the diol (L-menthol, 1-α-terpineol) showed much lower repellency against R. appendiculatus compared to p-menthane-3,8-diol stereoisomers. E. citriodora oil had much lower repellency than PMD stereoisomers, but signifi cantly higher repellency than L-menthol and 1-α-terpineol. This study concludes that menthane-diol stereoisomers and E. citriodora oil have potent repellency activity against the Brown Ear tick (Rhipicephalus appendiculatus) and can be used in the management of ticks and insects in livestock.