ABSTRACT
In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC50 values of 3.77 μmol·L-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.
ABSTRACT
Objective To identify potential linkage of cholesterol efflux with the expressions of ATP-binding cas-sette receptor A1 (ABCA1), ABCG1 and scavenger receptor B1 (SR-B1) in monocytes derived macrophages of patients with type 2 diabetes mellitus. Methods and Results Blood was collected from subjects with or without type 2 diabetes mellitus. Peripheral blood monocytes were differentiated for 72 hours into macrophages, and cholesterol efflux assays, Real-time quantitative PCR and western blot were performed. Macrophages from patients with type 2 diabetes mellitus showed a reduction in cholesterol efllux. The mRNA and protein expressions of ABCG1 in macrophages from patients with type 2 diabetes mellitus were significantly reduced. In contrast, the expression of ABCA1 and SR-B1 was not significantly different in both control subjects and diabetic patients. In addition, cellular cholesterol efflux from macrophages to autologous serum and pool serum was significantly correlated with the expression of ABCG1. Conclusion ABCG1 expression and cholesterol efflux are reduced in patients with type 2 diabetes mellitus. This impaired cholesterol efflux significantly correlates with decreased expression of ABCG1.
ABSTRACT
Objective To identify potential linkage of cholesterol efflux with the expressions of ATP-binding cassette receptor A1(ABCA1),ABCG1 and scavenger receptor B1(SR-B1) in monocytes derived macrophages of patients with type 2 diabetes mellitus.Methods and Results Blood was collected from subjects with or without type 2 diabetes mellitus.Peripheral blood monocytes were differentiated for 72 hours into macrophages,and cholesterol efflux assays,Real-time quantitative PCR and western blot were performed.Macrophages from patients with type 2 diabetes mellitus showed a reduction in cholesterol efflux.The mRNA and protein expressions of ABCG1 in macrophages from patients with type 2 diabetes mellitus were significantly reduced.In contrast,the expression of ABCA1 and SR-B1 was not significantly different in both control subjects and diabetic patients.In addition,cellular cholesterol efflux from macrophages to autologous serum and pool serum was significantly correlated with the expression of ABCG1.Conclusion ABCG1 expression and cholesterol efflux are reduced in patients with type 2 diabetes mellitus.This impaired cholesterol efflux significantly correlates with decreased expression of ABCG1.