Design, Synthesis and Photochemical Reactivation of Caged Prodrugs of 8-Hydroxyquinoline-Based Enzyme Inhibitors
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- Ariyasu Shinya
- Center for Technologies against Cancer, Tokyo University of Science
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- Mizuseda Yuki
- Faculty of Pharmaceutical Sciences, Tokyo University of Science
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- Hanaya Kengo
- Faculty of Pharmaceutical Sciences, Tokyo University of Science
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- Aoki Shin
- Center for Technologies against Cancer, Tokyo University of Science Faculty of Pharmaceutical Sciences, Tokyo University of Science
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Description
8-Hydroxyquinoline (HQ)-based compounds have recently been proposed as potential candidates for drugs for treating human immunodeficiency virus (HIV), cancer, neurodegenerative diseases (Alzheimer’s and Parkinson’s disease), and parasitic and bacterial infections. However, HQ itself and its derivatives might be toxic due to their intrinsic affinity for metal cations in living systems. One possible strategy for suppressing the toxicity and side effects of drugs with metal chelation properties, such as HQ, would be masking the critically important moieties with protecting groups that can be subsequently removed under specific conditions. In our previous work, we reported that HQ analogs are potent and selective inhibitors (Ki values=0.16–29 µM) of aminopeptidase from Aeromonas proteolytica (AAP) (EC 3.4.11.10), a dinuclear Zn2+ peptidase. Based on this background information, HQ sulfonates were synthesized as prodrugs of HQ-based AAP-inhibitors that can be reactivated by photochemical cleavage of the S–O bond in the sulfonate groups. The findings indicate that HQ sulfonates containing methanesulfonyl and 2-aminoethanesulfonyl groups are essentially stable under physiological conditions and undergo photolysis to regenerate the corresponding HQ compounds that function as AAP inhibitors. This methodology could be applied to the design of similar types of Zn2+ hydrolase inhibitors and prodrugs.
Journal
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- Chemical and Pharmaceutical Bulletin
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Chemical and Pharmaceutical Bulletin 62 (7), 642-648, 2014
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390001204176700416
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- NII Article ID
- 130004053800
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- NII Book ID
- AA00602100
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- COI
- 1:STN:280:DC%2BC2cfovFSksg%3D%3D
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- ISSN
- 13475223
- 00092363
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- NDL BIB ID
- 025543028
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- PubMed
- 24990501
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed