Synthesis, antifeedant activity against Coleoptera and 3D QSAR study of alpha-asarone derivatives.

For the first time, a set of 56 compounds representing structural derivatives of naturally occurring alpha-asarone as an antifeedants against stored product pests Sitophilus granarius L., Trogoderma granarium Ev., and Tribolium confusum Duv., were subjected to the 3D QSAR studies. Three-dimensional quantitative structure-activity relationships (3D-QSAR) for 56 compounds, including 15 newly synthesized, were performed using comparative molecular field analysis s-CoMFA and SOM-CoMSA techniques. QSAR was conducted based on a combination of biological activity (against Coleoptera larvae and beetles) and various geometrical, topological, quantum-mechanical, electronic, and chromatographic descriptors. The CoMSA formalism coupled with IVE (CoMSA-IVE) allowed us to obtain highly predictive models for Trogoderma granarium Ev. larvae. We have found that this novel method indicates a clear molecular basis for activity and lipophilicity. This investigation will facilitate optimization of the design of new potential antifeedants.

Synthesis and hypolipidemic and antiplatelet activities of alpha-asarone isomers in humans (in vitro), mice (in vivo), and rats (in vivo).

A series of alpha-asarone isomers was synthesized and investigated for their hypolipidemic and antiplatelet activity. Considering the hypolipidemic activity in rats at a dose of 80 mg/kg/day, some isomers were more potent than clofibrate at 150 mg/kg. Compound 3 was one of the most active agents elevating the HDL cholesterol level by 56% and lowering the LDL cholesterol level by 46.8% in rats after 7 days of administration. The activities of the platelet aggregation test in vitro were significant but lower than those of the reference substances (indomethacine and acetylsalicylic acid). In the pulmonary thromboembolic in vivo test in mice, two compounds (alpha-asarone (6) and compound 4) produced significant antithrombotic effects at 100 mg/kg, namely 44% and 52% protection against lung microembolia, respectively. alpha-Asarone derivatives form a new group of potential hypolipidemic and/or antithrombotic agents. The compounds 3, 4, and 6 may serve as lead substances whose structural modifications may result in original drugs.