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NAD(P)H:Quinone Acceptor Oxidoreductase 1 (NQO1) Activatable Salicylamide H+ /Cl- Transporters.
Roy, Naveen J; Save, Shreyada N; Sharma, Virender Kumar; Abraham, Benchamin; Kuttanamkuzhi, Abhijith; Sharma, Shilpy; Lahiri, Mayurika; Talukdar, Pinaki.
Afiliación
  • Roy NJ; Department of Chemistry, Indian Institute of Science Education and Research (IISER) Pune, Dr. Homi Bhabha Road, Pashan, Pune, 411008, Maharashtra, India.
  • Save SN; Department of Biotechnology, Savitribai Phule Pune University (Formerly University of Pune), Pune, 411007, Maharashtra, India.
  • Sharma VK; Department of Biology, Indian Institute of Science Education and Research (IISER) Pune, Dr. Homi Bhabha Road, Pashan, Pune, 411008, Maharashtra, India.
  • Abraham B; Department of Biology, Indian Institute of Science Education and Research (IISER) Pune, Dr. Homi Bhabha Road, Pashan, Pune, 411008, Maharashtra, India.
  • Kuttanamkuzhi A; Department of Biology, Indian Institute of Science Education and Research (IISER) Pune, Dr. Homi Bhabha Road, Pashan, Pune, 411008, Maharashtra, India.
  • Sharma S; Department of Biotechnology, Savitribai Phule Pune University (Formerly University of Pune), Pune, 411007, Maharashtra, India.
  • Lahiri M; Department of Biology, Indian Institute of Science Education and Research (IISER) Pune, Dr. Homi Bhabha Road, Pashan, Pune, 411008, Maharashtra, India.
  • Talukdar P; Department of Chemistry, Indian Institute of Science Education and Research (IISER) Pune, Dr. Homi Bhabha Road, Pashan, Pune, 411008, Maharashtra, India.
Chemistry ; 29(51): e202301412, 2023 Sep 12.
Article en En | MEDLINE | ID: mdl-37345998
ABSTRACT
NAD(P)Hquinone acceptor oxidoreductase 1 (NQO1), a detoxifying enzyme overexpressed in tumors, plays a key role in protecting cancer cells against oxidative stress and thus has been considered an attractive candidate for activating prodrug(s). Herein, we report the first use of NQO1 for the selective activation of 'protransporter' systems in cancer cells leading to the induction of apoptosis. Salicylamides, easily synthesizable small molecules, have been effectively used for efficient H+ /Cl- symport across lipid membranes. The ion transport activity of salicylamides was efficiently abated by caging the OH group with NQO1 activatable quinones via either ether or ester linkage. The release of active transporters, following the reduction of quinone caged 'protransporters' by NQO1, was verified. Both the transporters and protransporters exhibited significant toxicity towards the MCF-7 breast cancer line, mediated via the induction of oxidative stress, mitochondrial membrane depolarization, and lysosomal deacidification. Induction of cell death via intrinsic apoptotic pathway was verified by monitoring PARP1 cleavage.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / NAD Límite: Female / Humans Idioma: En Revista: Chemistry Asunto de la revista: QUIMICA Año: 2023 Tipo del documento: Article País de afiliación: India

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / NAD Límite: Female / Humans Idioma: En Revista: Chemistry Asunto de la revista: QUIMICA Año: 2023 Tipo del documento: Article País de afiliación: India