Non-food bioactive natural forest products as insecticide candidates: Preparation, biological evaluation and molecular docking studies of novel N-(1,3-thiazol-2- yl)carboxamides fused (+)-nootkatone from Chamaecyparis nootkatensis [D. Don] Spach

(+)-Nootkatone, a non-food bioactive natural bicyclic sesquiterpene ketone, is isolated from Chamaecyparis nootkatensis [D. Don] Spach as a renewable forest resource. In continuation of our effort to develop synthetic natural derived insecticides from non-food bioactive products, a small library of thirty N -(1,3- thiazol-2-yl)carboxamides fused (+)-nootkatone was prepared by molecular hybridization and characterized by 1 H/ 13 C NMR, HR-MS, and IR spectroscopy. Their insecticidal activities against Mythimna separata Walker and Plutella xylostella Linnaeus were evaluated. Compounds B6 , B7 , B9 , B19 – 21 and B24 showed better insecticidal activity against M. separata than the botanical insecticide azadirachtin , and their LC 50 values ranged from 0.55−0.68 mg/mL. Particularly, compound B9 exhibited 1.87-fold more pronounced insecticidal activity against M. separata than azadirachtin. The insecticidal activity of B21 against P. xylostella was 1.37-fold of that of azadirachtin. Through acetylcholinesterase (AChE) inhibitory activity and molecular docking studies, AChE may be the insecticidal target of B9 against M. separata . In addition, three pronounced compounds B9 , B21 and B24 exhibited low hemolytic and cytotoxic activities on normal mammalian cells. These findings will give insights into the further development of (+)-nootkatone derivatives as potentially synthetic natural derived insecticides for pest management.