살충제 개발에 있어 우선적으로 고려할 사항은 대상해충에 대한 우수한 살충활성과 포유동물에 대한 독성문제의 해결이다. 이러한 측면에서 두 가지 문제를 동시에 해결할 수 있는 대안 중의 하나는 곤충의 스테롤 대사와 관련한 작용기작을 갖는 것 이다. 곤충의 스테롤 대사 저해제에 착안하여 Acetyl Co-A:Colesterol acetyltransferase(이하 ACAT)을 새로운 작용점으로 하는 살충제의 개발은 곤충의 탈피, 변태, 에너지 생성, 난의 생성, 세포막 형성을 저해하는 살충활성을 가질 뿐만 아니라 포유동물에 대한 독성 문제도 해결 할 수 있을 것으로 판단된다. 기지의 연구에서는 ACAT에 대한 IC50 = 58nM ~ 16.0μM 수준의 활성을 갖는 4종의 물질을 Penicillium griseofulvum F-1959 로부터 분리하였으며, 이 물질들은 갈색거저리와 인시목 해충에 대한 살충활성이 우수한 것으로 보고되어 있다. 본 연구에서는 천연물을 근간으로 ACAT을 새로운 작용점으로 하는 새로운 구조의 화합물을 합성하였으며, 이를 배추좀나방(Plutella xylostella) 유충에 대하여 살충활성 검정하였으며, 10~100ppm에서 100%의 살충활성효과를 보였다.

Effect of perilla oil on the fatty acid composition, ACAT and HMG-CoA reductase in the liver microsomes, or cholesterol and protein in serum of rabbit were examined. 1. The content of total protein in serum was almost same amount of both groups, but α1-globulin and r-globuline were incresed or β-globulin was decresed compared with control. 2. The content of high density lipoprotein incresed, and the content of low density lipoprotein decresed in lipoprotein. 3. Total cholesterol and triglyceride were decresed, and the content of phospholipid was incresed. 4. Perilla oil did not effect for changing blood glucose and Na+, K+ electrolytes. 5. Perilla oil did not effect for changing serum GOT and GPT in rabbit. 6. The activity of ACAT decresed and the activity of HMG-CoA reductase incresed. The activity of ACAT and HMG-CoA reductase in liver microsomes were reciprocal. 7. There were arachidonic acid 20:4, eicosapentaenoic acid 20:5, and docosahexaenoic acid 22:6 in the liver microsomes of rabbits. These highly polyunsaturated fatty acids were convented from linolenic acid 18:3 n-3.

Acyltransferase (AT) catalyzes the transfer of an acyl moiety from acyl-coenzyme A (acyl-CoA) to an acceptor. ATs play important roles in the maintenance of homeostasis in the human body and have been linked to various diseases; therefore, several ATs have been proposed as potential targets for the treatment or prevention of such diseases. The AT family includes acyl-CoA:cholesterol AT (ACAT), diacylglycerol AT, and monoacylglycerol AT for the metabolism of lipids. Furthermore, recent molecular biological studies revealed the existence of their isozymes with distinct functions in the body. ACAT plays a critical role in the formation of cholesteryl esters from cholesterol and fatty acids, and is a potential target for treating hypercholesterolemia. During an experiment designed to discover biologically active compounds from herbal medicines, we isolated two known guaianolide sesquiterpene lactones from Chrysanthemum boreale Makino (Compositae). The lactones were characterized from their spectroscopic data (NMR, IR, MASS). These compounds were subjected to ACAT inhibition assay. Here, we report the isolation and structural elucidation of the compounds 8-o-acetyl-2-methoxy-10-hydroxy-3,11(13)-guaiadiene-12,6-olide and 8-acetyl-3,10-hydroxy-4(15),11(13)-guaiadiene-12,6-olide. In the ACAT inhibition assay, compound 1 showed strong inhibitory activity, with an IC50 value 45 μg/mL, whereas compound 2 did not exhibit significant inhibitory activity with an over 100 μg/mL.

Cholesterol acyltransferase (ACAT) catalyzes the acylation of cholesterol to cholesteryl ester with long chain fatty acids and ACAT inhibition is a useful strategy for treating hypercholesterolemia or atherosclerosis. Inhibitory effects on ACAT of the MeOH extracts prepared from 163 edible plants were evaluated. 15 species out of 163 species exhibited higher than 50% of inhibition on the hACAT-1 and 9 species exhibited higher than 50% of inhibition on the hACAT-2 activity at their concentration of 100 μg/mL.