Metabolism of drugs in the human body can yield both desirable and undesirable results. Some of these side-effects are due to drug-drug interactions, drug-diet interactions, or lack of specificity of drugs. The enzymes that drugs attack are structurally selective and complex, so many drugs are very general in structure and may react with a variety of enzymes. Indazole has become a backbone to several drugs as it has the general structure that may react with most p450s. To determine a derivative or a group of derivatives of indazole that may be reactive only with cytochrome p450 2E1 (CYP2E1) several indazole derivatives were employed as inhibitors to various p450s in enzyme-substrate reactions for IC50 assays. We hypothesized that the introduction of substituents to the indazole ring would retain high affinity for CYP2E1 while maintaining high selectivity against other p450s. The results of the IC50 assays will show which inhibitors react specifically with CYP2E1 but not with the other p450s. These findings will provide insight on the specificity of CYP2E1 and on some structure function issues with other p450s. The results of this project may lay groundwork for other experimentation, such as docking studies, and for the possibility of using indazole derivatives as scaffolding for drugs.

Assessing specificity of indazole derivatives as inhibitors to CYP2E1

253rd National Meeting (2017)

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