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Keywords:

  • bioorganic chemistry;
  • chalcogens;
  • heterocycles;
  • inhibitors;
  • scavengers

Abstract

Herein, we describe the synthesis and biomimetic activity of a series of N,N-disubstituted thiones and selones that contain an imidazole pharmacophore. The N,N-disubstituted thiones do not show any inhibitory activity towards LPO-catalyzed oxidation reactions, but their corresponding N,N-disubstituted selones exhibit inhibitory activity towards LPO-catalyzed oxidation reactions. Substituents on the N atom of the imidazole ring appear to have a significant effect on the inhibition of LPO-catalyzed oxidation and iodination reactions. Selones 16, 17, and 19, which contain methyl, ethyl, and benzyl substituents, exhibit similar inhibition activities towards LPO-catalyzed oxidation reactions with IC50 values of 24.4, 22.5, and 22.5 μM, respectively. However, their activities are almost three-fold lower than that of the commonly used anti-thyroid drug methimazole (MMI). In contrast, selone 21, which contains a N[BOND]CH2CH2OH substituent, exhibits high inhibitory activity, with an IC50 value of 7.2 μM, which is similar to that of MMI. The inhibitory activity of these selones towards LPO-catalyzed oxidation/iodination reactions is due to their ability to decrease the concentrations of the co-substrates (H2O2 and I2), either by catalytically reducing H2O2 (anti-oxidant activity) or by forming stable charge-transfer complexes with oxidized iodide species. The inhibition of LPO-catalyzed oxidation/iodination reactions by N,N-disubstituted selones can be reversed by increasing the concentration of H2O2. Interestingly, all of the N,N-disubstituted selones exhibit high anti-oxidant activities and their glutathione peroxidase (GPx)-like activity is 4–12-fold higher than that of the well-known GPx-mimic ebselen. These experimental and theoretical studies suggest that the selones exist as zwitterions, in which the imidazole ring contains a positive charge and the selenium atom carries a large negative charge. Therefore, the selenium moieties of these selones possess highly nucleophilic character. The 77Se NMR chemical shifts for the selones show large upfield shift, thus confirming the zwitterionic structure in solution.

Featured Compounds

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  1. 1 - 41
Compound 16
Molecular Weight:175.09
Molecular Formula:C5H8N2Se
InChIKey:PQKUSNASLKWMDE-UHFFFAOYSA-N
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Compound 17
Molecular Weight:189.12
Molecular Formula:C6H10N2Se
InChIKey:QPLFRXXOHSXFDG-UHFFFAOYSA-N
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Compound 19
Molecular Weight:251.19
Molecular Formula:C11H12N2Se
InChIKey:ZLCVZLRKUXQSBS-UHFFFAOYSA-N
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Compound 1
Molecular Weight:114.169
Molecular Formula:C4H6N2S
InChIKey:PMRYVIKBURPHAH-UHFFFAOYSA-N
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Compound 21
Molecular Weight:205.12
Molecular Formula:C6H10N2OSe
InChIKey:PQFAUCUZRGZZOG-UHFFFAOYSA-N
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Compound 3
Molecular Weight:170.232
Molecular Formula:C7H10N2OS
InChIKey:KNAHARQHSZJURB-UHFFFAOYSA-N
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Compound 5
Molecular Weight:186.231
Molecular Formula:C7H10N2O2S
InChIKey:CFOYWRHIYXMDOT-UHFFFAOYSA-N
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Compound 2
Molecular Weight:161.06
Molecular Formula:C4H6N2Se
InChIKey:CACMOFJOXKRQIJ-UHFFFAOYSA-N
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Compound 4
Molecular Weight:217.13
Molecular Formula:C7H10N2OSe
InChIKey:FRUDSHBPJSPQDQ-UHFFFAOYSA-N
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Compound 6
Molecular Weight:233.13
Molecular Formula:C7H10N2O2Se
InChIKey:JVNZPHJGADWYOA-UHFFFAOYSA-N
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Compound 15
Molecular Weight:128.195
Molecular Formula:C5H8N2S
InChIKey:ZYPLZLQKRFFKCL-UHFFFAOYSA-N
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Compound 18
Molecular Weight:204.291
Molecular Formula:C11H12N2S
InChIKey:SNNMDHJKWDABGM-UHFFFAOYSA-N
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Compound 20
Molecular Weight:158.221
Molecular Formula:C6H10N2OS
InChIKey:WPEOBRXNGISRHO-UHFFFAOYSA-N
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Compound 24
Molecular Weight:235.14
Molecular Formula:C7H12N2O2Se
InChIKey:XEIRZISFTMXVMU-UHFFFAOYSA-N
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Compound 22
Molecular Weight:112.1298
Molecular Formula:C5H8N2O
InChIKey:AMSDWLOANMAILF-UHFFFAOYSA-N
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Compound 7
Molecular Weight:224.0428
Molecular Formula:C5H9IN2
InChIKey:ARSMIBSHEYKMJT-UHFFFAOYSA-M
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Compound 8
Molecular Weight:191.069
Molecular Formula:C6H11BrN2
InChIKey:GWQYPLXGJIXMMV-UHFFFAOYSA-M
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Compound 9
Molecular Weight:208.687
Molecular Formula:C11H13ClN2
InChIKey:FCRZSGZCOGHOGF-UHFFFAOYSA-M
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Compound 10
Molecular Weight:162.617
Molecular Formula:C6H11ClN2O
InChIKey:QVRFXIWAQRNWEX-UHFFFAOYSA-M
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Compound 23
Molecular Weight:192.643
Molecular Formula:C7H13ClN2O2
InChIKey:ZRVVMYXNYLDCJH-UHFFFAOYSA-M
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Compound 27
Molecular Weight:348.16
Molecular Formula:C10H14N4Se2
InChIKey:WVHOHFMKJRNAMO-UHFFFAOYSA-N
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Compound 28
Molecular Weight:406.567
Molecular Formula:C22H22N4S2
InChIKey:WFCJYBQXTXKLCJ-UHFFFAOYSA-N
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Compound 29
Molecular Weight:500.36
Molecular Formula:C22H22N4Se2
InChIKey:LQKKWQJOVXXLKN-UHFFFAOYSA-N
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Compound 32
Molecular Weight:330.471
Molecular Formula:C16H18N4S2
InChIKey:LAMIZYXVOJHVFZ-UHFFFAOYSA-N
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Compound 33
Molecular Weight:424.26
Molecular Formula:C16H18N4Se2
InChIKey:VRXSINCUSLNTPB-UHFFFAOYSA-N
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Compound 34
Molecular Weight:484.31
Molecular Formula:C18H22N4O2Se2
InChIKey:UJRLTFJAZHQBRS-UHFFFAOYSA-N
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Compound 36
Molecular Weight:498.73
Molecular Formula:C24H30N6S3
InChIKey:XVUOMTBBXHZKDE-UHFFFAOYSA-N
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Compound 37
Molecular Weight:639.42
Molecular Formula:C24H30N6Se3
InChIKey:RZUUGBCARORMCD-UHFFFAOYSA-N
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Compound 25
Molecular Weight:352.069
Molecular Formula:C10H16Br2N4
InChIKey:KFDWMMRHEBCWFL-UHFFFAOYSA-L
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Compound 26
Molecular Weight:504.261
Molecular Formula:C22H24Br2N4
InChIKey:UVZXYRSTUQGLAJ-UHFFFAOYSA-L
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Compound 35
Molecular Weight:645.271
Molecular Formula:C24H33Br3N6
InChIKey:ICRIRRJGUIJSNK-UHFFFAOYSA-K
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Compound 41
Molecular Weight:177.11
Molecular Formula:C5H10N2Se
InChIKey:NDRDWKIFFOCDJI-UHFFFAOYSA-N
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Compound 42
Molecular Weight:301.25
Molecular Formula:C15H14N2Se
InChIKey:VKAVMYFGWYKWQL-UHFFFAOYSA-N
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Compound 43
Molecular Weight:261.27
Molecular Formula:C11H22N2Se
InChIKey:OKWRAZWUMKHCRB-UHFFFAOYSA-N
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Compound 38
Molecular Weight:88.1515
Molecular Formula:C4H12N2
InChIKey:Not Available
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Compound 39
Molecular Weight:212.2902
Molecular Formula:C14H16N2
InChIKey:NOUUUQMKVOUUNR-UHFFFAOYSA-N
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Compound 40
Molecular Weight:172.311
Molecular Formula:C10H24N2
InChIKey:KGHYGBGIWLNFAV-UHFFFAOYSA-N
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Compound 30
Molecular Weight:428.165
Molecular Formula:C16H20Br2N4
InChIKey:PTAZJSZTEMWQDC-UHFFFAOYSA-L
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Compound 31
Molecular Weight:488.217
Molecular Formula:C18H24Br2N4O2
InChIKey:XFEQLNFZPAOXRL-UHFFFAOYSA-L
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Compound 44
Molecular Weight:756.18
Molecular Formula:C22H24I2N4Se2
InChIKey:GCNVACSIYGOTTI-UHFFFAOYSA-L
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Compound 45
Molecular Weight:505
Molecular Formula:C11H12I2N2Se
InChIKey:TVIKSNPLZZOSDD-UHFFFAOYSA-N
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