Dinuclear complex [Ir₂(μ-L1)(η⁵-Cp*)₂Cl₂](PF₆)₂ (1) exhibits low micromolar cytotoxic activity in vitro in various human cancer cells (GI₅₀ = 1.7-3.0 μM) and outperformed its mononuclear analogue [Ir(η⁵-Cp*)Cl(L2)]PF₆ (2; GI₅₀ > 40.0 μM); Cp* = pentamethylcyclopentadienyl, L1 = 4-chloro-2,6-bis[5-(pyridin-2-yl)-1,3,4-thiadiazol-2-yl]pyridine, L2 = 5-(pyridin-2-yl)-1,3,4-thiadiazol-2-amine. Compound 1 upregulated the Keap1/Nrf2 oxidative stress-protective pathway in the treated MV4-11 acute myeloid leukemia cells. In connection with the redox-mediated mode of action of 1, its NADH-oxidizing activity was detected in solution (¹H NMR), while NAD⁺ remained intact (with formate as a hydride source). Surprisingly, only negligible NADH oxidation was detected in the presence of the reduced glutathione and ascorbate. Following the results of in-solution experiments, NAD(H) concentration was assessed in 1-treated MV4-11 cancer cells. Besides the intracellular NADH oxidation in the presence of 1, the induced oxidative stress also led to a decrease of NAD⁺, resulting in depletion of both NAD⁺/NADH coenzymes. The discussed findings provide new insight into the biochemical effects of catalytic anticancer compounds that induce cell death via a redox-mediated mode of action.

2024-12-01·Archivos Argentinos de Pediatria

Post-infectious pityriasis rubra pilaris in pediatric patients

Article

作者: Arellano, Javier ; Melehuechun, Catalina

Pityriasis rubra pilaris (PRP) is a rare skin condition. The etiology of PRP is unknown; however, it has been associated with infections, autoimmune diseases, and neoplasms. Here we describe the cases of 2 pediatric patients with PRP triggered by a respiratory syncytial virus infection concurrently with obstructive bronchial syndrome. PRP resolved after treatment with topical emollients, topical corticosteroids, and calcineurin inhibitors.

2024-11-01·Microbiological Research

Repurposing cetylpyridinium chloride and domiphen bromide as phosphoethanolamine transferase inhibitor to combat colistin-resistant Enterobacterales

Article

作者: Kin So, Pui ; Chen, Kaichao ; Wong, Kwok-Yin ; Cheng, Qipeng ; Gu, Yanjuan ; Chan, Edward Wai Chi ; kin So, Pui ; Wong, Iris Lai-King ; Wong, Iris Lai-king ; Chen, Sheng ; Xu, Chen ; Chan, Kin Fai ; Jin, Wenbin

100 项与 Transferase inhibitors(Merck) 相关的药物交易

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