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Demonstration of the hypoglycemic action of Momordica charantia in a validated animal model of diabetes. Hypoglycaemic activity of Coccinia indica and Momordica charantia in diabetic rats: depression of the hepatic gluconeogenic enzymes glucose-6-phosphatase and fructose-1,6-bisphosphatase and elevation of both liver and red-cell shunt enzyme glucose-6-phosphate dehydrogenase. Role of aldose reductase and oxidative damage in diabetes and the consequent potential for therapeutic options. Structural elucidation and cellular antioxidant activity evaluation of major antioxidant phenolics in lychee pulp. Silymarin as a natural antioxidant: an overview of the current evidence and perspectives. Immunohistochemical study of apoptosis of lens epithelial cells in human and diabetic rat cataracts. Outbreaks of hypoglycemic encephalopathy in Muzaffarpur, India: Are these caused by toxins in litchi fruit Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. Silymarin reduces hyperinsulinemia, malondialdehyde levels, and daily insulin need in cirrhotic diabetic patients. Silymarin in Type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Hypoglycemic, interferonogenous, and immunomodulatory activity of Tremellastin from the submerged culture of Tremella mesenterica Retz. A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome. Effect of Momordica charantia on the glucose tolerance in maturity onset diabetes. In vitro antidiabetic effects of selected fruits and vegetables against glycosidase and aldose reductase. Slow acting protein extract from fruit pulp of Momordica charantia with insulin secretagogue and insulinomimetic activities. The effect of bitter melon (Momordica charantia) in patients with diabetes mellitus: a systematic review and meta-analysis. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Phenolic profiles and antioxidant activity of litchi pulp of different cultivars cultivated in Southern China.
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This is achieved by the creation of two different possible pockets capable of accommodating aromatic substituents. Moreover, flexibility within the pockets themselves allows binding of differently sized substituents. It is possible that the pi-stacking interactions involving Phe188, the inhibitor, and other amino acid residues plays a crucial role in driving protein flexibility. The subsequent addition of a methyl group to the benzimidazole ring resulted in structure 37, which was comparable in activity, and had a marked improvement in metabolic stability. It also showed single-digit nanomolar inhibition on the growth of 3D7 strains of P. The cyclopropyl group binds to a mainly hydrophobic pocket, while the amide group interacts through two hydrogen bonds with His185 and Arg265. The benzimidazole ring is orientated toward the protein surface and occupies the hydrophobic pocket involved in pi-stacking interactions. In this case, there is an edge-to-face interaction between the benzimidazole ring and the aromatic ring of Phe188. It was then hypothesized that molecules containing an N-methyl substituent would favor a non-planar conformation to avoid intramolecular steric clashes, and that such a conformation would be selective for the cylindrical binding site of the parasite enzyme. In contrast, structures with the unsubstituted nitrogen would favor a planar conformation because of extended conjugation, resulting in selectivity for the human enzyme. A number of these analogs were synthesized and tested as a proof-of-principle exercise. A bicyclic system or a large alkyl group at the para position of the phenyl ring was favored, as either moiety fills a hydrophobic pocket in the binding site. A hydrophilic group at position 3 of a dihydrothiophenone or dihydrofuranone ring was essential, and an ethyl ester is optimal. The compound was also an effective inhibitor of parasite growth in vitro, making it a promising lead compound for further investigations. The dihydrothiophene scaffold and its substituents occupy a hydrophilic region where hydrogen bonds are formed to Arg265, His185 and a water molecule (W15). There are significant molecular and functional differences between the two enzymes, which indicate that it should be possible to design drugs with species specificity. To determine the structure-activity relationships within the series, analogs were prepared with various substituents (R1) on the phenyl ring. For example, incorporating nitrogen into the benzene ring of the quinolone core was not tolerated well. Unfortunately, the compounds had poor aqueous solubility and it was hypothesized that this was due to the molecules adopting a planar conformation in which they formed intermolecular - interactions with each other. Molecular modelling predicted that a substituent placed at position 3 would act as a conformational blocker and prevent the aromatic ring at position 2 becoming coplanar with the quinolone ring. Further investigations revealed that the methyl group at position 3 was the optimum substituent.
