Molecules, Vol. 25, Pages 2004: Synthetic Kavalactone Analogues with Increased Potency and Selective Anthelmintic Activity against Larvae of Haemonchus contortus In Vitro

Molecules, Vol. 25, Pages 2004: Synthetic Kavalactone Analogues with Increased Potency and Selective Anthelmintic Activity against Larvae of Haemonchus contortus In Vitro Molecules doi: 10.3390/molecules25082004 Authors: H.M.P. Dilrukshi Herath Aya C. Taki Nghi Nguyen José Garcia-Bustos Andreas Hofmann Tao Wang Guangxu Ma Bill C.H. Chang Abdul Jabbar Brad E. Sleebs Robin B. Gasser Kava extract, an aqueous rhizome emulsion of the plant Piper methysticum, has been used for centuries by Pacific Islanders as a ceremonial beverage, and has been sold as an anxiolytic agent for some decades. Kavalactones are a major constituent of kava extract. In a previous investigation, we had identified three kavalactones that inhibit larval development of Haemonchus contortus in an in vitro-bioassay. In the present study, we synthesized two kavalactones, desmethoxyyangonin and yangonin, as well as 17 analogues thereof, and evaluated their anthelmintic activities using the same bioassay as employed previously. Structure activity relationship (SAR) studies showed that a 4-substituent on the pendant aryl ring was required for activity. In particular, compounds with 4-trifluoromethoxy, 4-difluoromethoxy, 4-phenoxy, and 4-N-morpholine substitutions had anthelmintic activities (IC50 values in the range of 1.9 to 8.9 µM) that were greater than either of the parent natural products—desmethoxyyangonin (IC50 of 37.1 µM) and yangonin (...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research