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Metformin (1,1-dimethylbiguanide) is an anti-hyperglycemic agent that is commonly used in the oral treatment of Type 2 Diabetes Mellitus. Phenformin (phenethylbiguanide) is its structural analog. In addition to their anti-hyperglycemic effects, both metformin and phenformin are known to inhibit proliferation of cancer cells. Adenosine deaminase is involved in purine nucleoside metabolism and its activity was elevated in certain cancers such as bladder and renal carcinoma, a possible cause for the proliferation of these cancer cells. Based on molecular docking simulations, we have hypothesized that adenosine deaminase could be inhibited by metformin and phenformin, and that phenformin is a better inhibitor than metformin. The inhibitory effect of metformin and phenformin on adenosine deaminase from bovine spleen was studied spectrophotometrically. Non-linear regression analysis was used to obtain the inhibition constants. Metformin was a competitive inhibitor of deamination of adenosine with the inhibition constant, KI, of 88 mM. Phenformin was slightly more effective than metformin as a competitive inhibitor with KI of 10 mM. The KM of adenosine was 31 μM. The inhibition constant values indicate that neither metformin nor phenformin is a potent inhibitor of adenosine deaminase. It is unlikely that at the physiological concentration, adenosine deaminase activity would be greatly affected by either drug.

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Poster, Final Report Form, Research Report

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Myoung Lee



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