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Caging Bioactive Triarylimidazoles: An Approach to Create Visible Light-Activatable Drugs.
Qi, Jiajun; Amrutha, Ammathnadu S; Ishida-Ishihara, Sumire; Dokainish, Hisham M; Hashim, P K; Miyazaki, Ryu; Tsuda, Masumi; Tanaka, Shinya; Tamaoki, Nobuyuki.
Afiliação
  • Qi J; Research Institute for Electronic Science, Hokkaido University, Kita 20, Nishi 10, Kita-ku, Sapporo, Hokkaido 001-0020, Japan.
  • Amrutha AS; Graduate School of Life Science, Hokkaido University, Kita 10, Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0810, Japan.
  • Ishida-Ishihara S; Research Institute for Electronic Science, Hokkaido University, Kita 20, Nishi 10, Kita-ku, Sapporo, Hokkaido 001-0020, Japan.
  • Dokainish HM; Graduate School of Life Science, Hokkaido University, Kita 10, Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0810, Japan.
  • Hashim PK; Graduate School of Life Science, Hokkaido University, Kita 10, Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0810, Japan.
  • Miyazaki R; Faculty of Advanced Life Science, Hokkaido University, Kita 21, Nishi 11, Kita-ku, Sapporo, Hokkaido 001-0021, Japan.
  • Tsuda M; Center of Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.
  • Tanaka S; Research Institute for Electronic Science, Hokkaido University, Kita 20, Nishi 10, Kita-ku, Sapporo, Hokkaido 001-0020, Japan.
  • Tamaoki N; Graduate School of Life Science, Hokkaido University, Kita 10, Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0810, Japan.
J Am Chem Soc ; 146(26): 18002-18010, 2024 Jul 03.
Article em En | MEDLINE | ID: mdl-38905195
ABSTRACT
Imidazoles are crucial structural components in a variety of small-molecule inhibitors designed to target different kinases in anticancer treatment. However, the effectiveness of such inhibitors is often hampered by nonspecific effects and the development of resistance. Photopharmacology provides a compelling solution by enabling external control over drug activity with spatiotemporal precision. Herein, we introduce a novel strategy for caging bioactive triarylimidazole-based drug molecules. This approach involves introducing a dialkylamino group as a photoremovable group on the carbon atom of the imidazole ring, which intrinsically modulates the core structure from planar imidazole to tetrahedral 2H-imidazole, enabling the caged compound to be selectively uncaged upon visible light exposure. We applied this innovative caging technique to SB431542, a triarylimidazole-based small-molecule inhibitor that targets the pivotal TGF-ß signaling pathway, the dysregulation of which is linked to several human diseases, including cancer. Our results demonstrated the selective inhibition of human breast cancer cell migration in vitro upon light activation, highlighting the potential of our approach to transform triarylimidazole-based drug molecules into visible light-activatable drugs, thereby facilitating spatiotemporal regulation of their pharmacological activity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Imidazóis / Luz Limite: Humans Idioma: En Revista: J Am Chem Soc Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Japão País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Imidazóis / Luz Limite: Humans Idioma: En Revista: J Am Chem Soc Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Japão País de publicação: Estados Unidos