nan Mustofa

Design and synthesis of chalcone derivatives as inhibitors of the ferredoxin - ferredoxin-NADP+ reductase interaction of Plasmodium falciparum: pursuing new antimalarial agents.

Some chalcones have been designed and synthesized using Claisen-Schmidt reactions as inhibitors of the ferredoxin and ferredoxin-NADP+ reductase interaction to pursue a new selective antimalaria agent. The synthesized compounds exhibited inhibition interactions between PfFd-PfFNR in the range of 10.94%–50%. The three strongest inhibition activities were shown by (E)-1-(4-aminophenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (50%), (E)-1-(4-aminophenyl)-3-(2,4-dimethoxyphenyl)prop-2-en-1-one (38.16%), and (E)-1-(4-aminophenyl)-3-(2,3-dimethoxyphenyl)prop-2-en-1-one (31.58%). From the docking experiments we established that the amino group of the methoxyamino chlacone derivatives plays an important role in the inhibition activity by electrostatic interaction through salt bridges and that it forms more stable and better affinity complexes with FNR than with Fd.

Effect of 7-Hydroxy-2-(4-Hydroxy-3-Methoxy-Phenyl)-Chroman-4-One (Swietenia Macrophylla King Seed) on Retinol Binding Protein-4 and Phosphoenolpyruvate Carboxykinase Gene Expression in Type 2 Diabetic Rats

Abstract Background and Aims: Diabetes mellitus is a metabolic disorder characterized by hyperglycemia due to a defect of insulin secretion, insulin action, or both. There are increasing evidence that active compounds of medicinal plants may be used to treat diabetes. The aim of this study is to investigate the effect of a 7-hydroxy-2-(4-hydroxy-3-methoxy-phenyl)-chroman-4-one flavonoid compound of the Swietenia macrophylla King seed on homeostatic model assessment of insulin resistance (HOMA-IR), phosphoenolpyruvate carboxykinase (PEPCK) and retinol binding protein-4 (RBP4) gene expression in diabetic rats. Materials and Method: Thirty Wistar rats were used with 5 in each group as follows: 1) normal rats; 2) diabetic rats; 3) diabetic rats with metformin; 4), 5) and 6) diabetic rats with a 7-hydroxy-2-(4-hydroxy-3-methoxy-phenly)-chroman-4-one 10, 30 and 90 mg/200 g body weight (BW) respectively. Blood glucose and insulin levels were analyzed before and after treatment. At the end of the study, the liver tissue was removed for quantitative PCR (qPCR) analyses. Results: Blood glucose levels decreased significantly (p<0.05) in diabetic rats with metformin and three different dosages of 7-hydroxy-2-(4-hydroxy-3-methoxy-phenly)-chroman-4-one. Insulin levels increased significantly (p<0.05) in diabetic rats with metformin and diabetic rats with 10 mg/200 g BW of 7-hydroxy-2-(4-hydroxy-3-methoxy-phenly)-chroman-4-one. HOMA-IR value decreased significantly (p<0.05) in diabetic rats with metformin and three different dosages of 7-hydroxy-2-(4-hydroxy-3-methoxy-phenly)-chroman-4-one. There was a significant decrease of PEPCK gene expression in the group with 90 mg/200 g BW of 7-hydroxy-2-(4-hydroxy-3-methoxy-phenly)-chroman-4-one. RBP4 gene expression showed a decline, but the difference between groups was not statistically different. Conclusion: These results demonstrated that 7-hydroxy-2-(4-hydroxy-3-methoxy-phenly)-chroman-4-one increased insulin and decreased blood glucose level, HOMA-IR value and PEPCK gene expression.