Reductase inhibitory activity

The triterpenoid constituents, 3p,22(3-dihydroxyolean-12-en-29-oic acid (85), tingenone (86), tingenine B (87 22(3-hydroxytingenone), regeol A (88) and triptocalline A (89) isolated from Salacia chinensis L. (family Celastraceae), were examined on rat lens for aldose reductase inhibitory activity the test compounds 85-89 were evaluated to exhibit rat lens aldose reducatse inhibitory activity with IC50 values of 26,13, 7.0,30, and 14 /rM, respectively. ... 

Lee H-S. (2002) Rat lens aldose reductase inhibitory activities of Coptis japonica root-derived isoquinoline alkaloids. JAgric Food Chem 50 7013-7016. 

Yoshikawa M, Nishida N, Shimoda H, Takada M, Kawahara Y, Matsuda H. (2001) Polyphenol constituents from Salacia Species Quantitative analysis of mangiferin with a-glucosidase and aldose reductase inhibitory activities. Yakugaku Zasshi 121 371-378. 

Cannabis sativa L. (marijuana) IX. Lens aldose reductase inhibitory activity of CSl33 marijuana flavone c-glycosides. 

The risk of myopathy appears to be increased by high levels of HMG-CoA reductase inhibitory activity in plasma. Lovastatin is metabolized by the CYP isoform 3A4. Certain drugs, that share this metabolic pathway can raise the plasma levels of lovastatin and may increase the risk of myopathy. These include cyclosporine, itraconazole, ketoconazole and other antifungal azoles, the macrolide antibiotics erythromycin and clarithromycin, HIV protease inhibitors, the antidepressant nefazodone, or large quantities of grapefruit juice (greater than 1 quart daily)... 

Sarges, R. Lyga, J. W. Synthesis and Aldose Reductase Inhibitory Activity of N-l,N-4-Disubstituled 3,4-Dihydro-2(lH)-quinoxalinone Derivatives, J. 

Atorvastatin is extensively metabolized to its ortho- and para-hyd roxylated derivatives, and to various beta oxidation products. At least 70% of HMG-CoA reductase inhibitory activity has been attributed to the active metabolites of atorvastatin. 

D. Natural Products with 5a-Reductase Inhibitory Activity. 172... 

A number of natural products reportedly possessing 5a-reductase inhibitory activity have been advocated for use in the treatment of andro-... 

Cactus flower extracts have also been reputed to be of benefit in the treatment of men with BPH, although there are no published studies regarding their clinical effects. A recent study demonstrated such extracts to have 5a-reductase inhibitory activity in cultured foreskin fibroblasts, and also in human placental and prostatic homogenates (Jonas et al., 1998). Cernilton, a pollen extract, has also been reported to have an inhibitory effect on 5a-reductase activity (Tunn and Krieg, 1992)... 

Some indolylthiohydantoin derivatives that have aldose reductase inhibitory activity [75] were investigated electroanalytically by voltammetric determination. Based on this study, a simple, rapid, sensitive and validated voltammetric method was developed for the determination of the compounds that are readily oxidized at carbon-based electrodes. Oxidation of the indolic compounds occurs on the nitrogen atom in the indole ring of the molecule [162]. 

Chlorophorin from Artocarpus incisus showed potent 5a-reductase inhibitory activity than its natural inhibitor, a-linolenic acid. Artocarbene (72) showed moderate effect. SAR investigations revealed that the presence of an isoprene substituent (prenyl and geranyl) would enhance 5a-reductase inhibitory effects [523]. 

Maccari, R., Ottana, R., Ciurleo, R., Vigorita, M. G., Rakowitz, D., Steindl, X, Langer, X. Evaluation of in vitro aldose reductase inhibitory activity of 5-arylidene-2,4-thiazolidinediones. Bioorg. Med. Chem. Lett. 2007,17, 3886-3893. 

Prabhakar, Y.S., Gupta, M.K., Roy, N. and Venkateswarlu, Y. (2005) Ahigh dimensional QSAR study on the aldose reductase inhibitory activity of some flavones topological descriptors in modeling the activity. J, Chem, Inf, Model., 46, 86-92. 

Toropoy A.A., Nesterov, I.V. and Nabiev, O.M. (2003a) QSAR modeling of dihydrofolate reductase inhibitory activity by correlation weighting of nearest neighboring codes. J. Mol. Struct. (Theochem), 622, 269-273. 

Glucosidase, Invertase and Aldose Reductase Inhibitory Activity... 

Table 8. Aldose Reductase Inhibitory Activity of Compounds 72 - 87...

Monacolins J (7), L (8), M (9) and X (10), dihydromonacolin L (11) and 3a-hydroxy-3,5-dihydromonacolin L acid (12) were isolated from cultures of M. ruber [31-34]. Mevinolinic acid (13) and dihydromevinolin (14) were produced by A. terreus [27,35]. Of them, HMG-CoA reductase inhibitory activities of dihydrocompactin and dihydromevinolin were comparable to those of mevastatin and lovastatin [36]. 

Tetramethyleneglutaric acid (TMG) (62) and alrestatin (AY-22,284) (63)) are known aldose reductase inhibitors. From natural products, a number of flavonoids have been reported to have aldose reductase inhibitory activity. Quercetin (64 1, R = H), quercitrin (64 2, R = L-rhamnose), rutin (64 3, R = rutinose (6-O-a -L-rhamnosyl-D-glucose)) and myricitrin (65 2, R = L-rhamnose) were much more effective inhibitors of aldose reductase from rat lens than TMG (62) and alrestatin (63) [66]. Quercetin with 3, 4 -dihydroxy substitution in ring C was more potent... 

After oral administration, intestinal absorption of the statins varies between 30% and 85%. All of the statins, except simvastatin and lovastatin, are administered as active ffhydroxy acids. Simvastatin and lovastatin are administered as inactive lactones that must be transformed in the liver to their respective ffhydroxy acids. There is extensive first-pass hepatic uptake of all statins, but they enter the liver by different mechanisms. Uptake of atorvastatin, pravastatin, and rosuvastatin is mediated by the organic anion transporter 2 (OATP2). The lipophilic lactone forms of simvastatin and lovastatin are thought to enter the liver by simple diffusion. Due to extensive first-pass hepatic uptake, systemic bioavailability of the statins and their hepatic metabolites varies between 5% and 30% of administered doses. Except for fluvastatin and pravastatin, the metabolites of all statins have some HMG-CoA reductase inhibitory activity. Under steady-state conditions, small amounts of the parent drug and its metabolites produced in the liver can be found in the systemic circulation. In the plasma, >95% of statins and their metabolites are protein bound with the exception of pravastatin and its metabolites (50% bound). 

Arnadottir M, Eriksson LO, Thysell H, Karkas JD. Plasma concentration profiles of simvastatin 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitory activity in kidney transplant recipients with and without ciclosporin. Nephron 1993 65 410-113. 

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