AI Article Synopsis

  • A series of novel imidazole-dioxolane compounds were created and tested for their ability to inhibit heme oxygenase (HO) enzymes, specifically targeting the stress-induced HO-1 and constitutive HO-2 isoforms.
  • Most of these compounds showed strong inhibitory effects, with some demonstrating moderate selectivity for HO-1, while others exhibited high selectivity.
  • Additionally, the study noted that larger substituents in the northeastern region of the structure did not inhibit CYP2E1, but a smaller fluorine-containing compound did, and all compounds displayed significant inhibition against CYP3A1/3A2.

Article Abstract

Several imidazole-dioxolane compounds were synthesized and evaluated as novel inhibitors of heme oxygenase (HO). These compounds, which include a series of substituted thiophenol and substituted phenol derivatives of (2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(phenylsulfanyl)methyl]-1,3-dioxolane hydrochloride (3), in addition to smaller functionalized derivatives, continue our structure-activity studies by exploration of the aminothiophenol region ('northeastern region') in our original target structure azalanstat (1). In vitro, most of the compounds in this series were found to be highly potent inhibitors of the stress-induced isozyme HO-1 and the constitutive isozyme HO-2, showing only moderate selectivity for HO-1. Nevertheless, a few of the compounds displayed higher selectivity toward HO-1. None of the compounds having a larger appendage in the northeastern region were inhibitors of CYP2E1, whereas a compound having a relatively small fluorine substituent in this region did inhibit CYP2E1; all of the compounds tested exhibited high inhibitory potency against CYP3A1/3A2.

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http://dx.doi.org/10.1016/j.bmc.2009.01.078DOI Listing

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