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2.
Org Biomol Chem ; 22(31): 6288-6293, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39041174

RESUMO

We present a new strategy for the dearomatized hydroxylation of 5-aminopyrazoles using a hypervalent iodine reagent at room temperature. This method produces a series of 4-hydroxy-5-iminopyrazolines with good to excellent yields within 2 hours. Additionally, we demonstrate a domino reaction for the synthesis of 4-hydroxy-pyrazolones. Mechanistic studies indicate that the dearomatization proceeds through a cationic intermediate.

3.
Redox Biol ; 73: 103219, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38851001

RESUMO

Radiation causes damage to normal tissues that leads to increased oxidative stress, inflammation, and fibrosis, highlighting the need for the selective radioprotection of healthy tissues without hindering radiotherapy effectiveness in cancer. This study shows that adiponectin, an adipokine secreted by adipocytes, protects normal tissues from radiation damage invitro and invivo. Specifically, adiponectin (APN) reduces chronic oxidative stress and fibrosis in irradiated mice. Importantly, APN also conferred no protection from radiation to prostate cancer cells. Adipose tissue is the primary source of circulating endogenous adiponectin. However, this study shows that adipose tissue is sensitive to radiation exposure exhibiting morphological changes and persistent oxidative damage. In addition, radiation results in a significant and chronic reduction in blood APN levels from adipose tissue in mice and human prostate cancer patients exposed to pelvic irradiation. APN levels negatively correlated with bowel toxicity and overall toxicities associated with radiotherapy in prostate cancer patients. Thus, protecting, or modulating APN signaling may improve outcomes for prostate cancer patients undergoing radiotherapy.


Assuntos
Adiponectina , Fibrose , Estresse Oxidativo , Neoplasias da Próstata , Masculino , Animais , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Humanos , Camundongos , Estresse Oxidativo/efeitos da radiação , Adiponectina/metabolismo , Adiponectina/sangue , Lesões por Radiação/metabolismo , Lesões por Radiação/patologia , Tecido Adiposo/metabolismo , Tecido Adiposo/efeitos da radiação , Protetores contra Radiação/farmacologia , Protetores contra Radiação/uso terapêutico
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