Structure-activity relationship studies on the mosquito toxicity and biting deterrency of callicarpenal derivatives.
Callicarpenal (=13,14,15,16-tetranorclerod-3-en-12-al=[(1S,2R,4aR,8aR)-1,2,3,4,4a,7,8,8a-octahydro-1,2,4a,5-tetramethylnaphthalen-1-yl]acetaldehyde; 1) has previously demonstrated significant mosquito bite-deterring activity against Aedes aegypti and Anopheles stephensi in addition to repellent activity against host-seeking nymphs of the blacklegged tick, Ixodes scapularis. In the present study, structural modifications were performed on callicarpenal (1) in an effort to understand the functional groups necessary for maintaining and/or increasing its activity and to possibly lead to more effective insect control agents. All modifications in this study targeted the C(12) aldehyde or the C(3) alkene functionalities or combinations thereof. Mosquito biting deterrency appeared to be influenced most by C(3) alkene modification as evidenced by catalytic hydrogenation that resulted in a compound having significantly less effectiveness than 1 at a test amount of 25 nmol/cm2. Oxidation and/or reduction of the C(12) aldehyde did not diminish mosquito biting deterrency, but, at the same time, none of the modifications were more effective than 1 in deterring mosquito biting. Toxicities of synthesized compounds towards Ae. aegypti ranged from an LD50 value of 2.36 to 40.11 microg per mosquito. Similarly, LD95 values ranged from a low of 5.59 to a high of 104.9 microg.
USDA-ARS, Natural Products Utilization Research Unit, University, MS 38677, USA. charles.cantrell@ars.usda.gov
Charles L
CL
Cantrell
Jerome A
JA
Klun
Julia
J
Pridgeon
James
J
Becnel
Solomon
S
Green
Frank R
FR
Fronczek
D000330:Aedes / Q000187:drug effects*; D000818:Animals; D000852:Anopheles / Q000187:drug effects*; D018360:Crystallography, X-Ray; D005260:Female; D007299:Insect Bites and Stings; D007302:Insect Repellents / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity
D007302:Insect Repellents; D013729:Terpenes; C523653:callicarpenal