Identification of novel N-acetylcysteine derivatives for the treatment of hepatocellular injury

Abstract

New anti-hepatocellular injury drugs with better curative effects and fewer side effects are urgently needed at present. In this study, a series of novel -acetylcysteine (NAC) derivatives were designed, synthesized and biologically evaluated for their anti-hepatocellular injury activities against two different cell models. In the biological evaluation against hydrogen peroxide (HO)-induced LO2 hepatocytes, half of the target compounds exhibited moderate to potent activities in improving the model cell viability, and two compounds ( and ) displayed more potent activities in decreasing malondialdehyde (MDA) levels than the positive control NAC. In further 4-acetamidophenol (APAP)-induced LO2 cell experiment, compounds and could not only improve the cell viability but also significantly reduce the secretion of MDA. Additionally, compound displayed excellent Caco-2 permeability and oral bioavailability in rats. All these experimental results suggested that compounds and could serve as potential lead molecules for further development of anti-hepatocellular injury drugs.

Continuous Monitoring Reveals Protective Effects of N‐Acetylcysteine Amide on an Isogenic Microphysiological Model of the Neurovascular Unit

“…While the literature does not provide prior in vitro examples for NACA, one study with an epithelial Caco‐2 barrier model has reported P app for NAC below their assay detection limit (≈5−10 nm s −1 ). [ 58 ] Compared to hiBMEC, Caco‐2 are typically leakier (e.g., 13 vs <2.5 nm s −1 for sodium fluorescein). [ 8,59 ] Taken together, this may indicate that indeed NACA features higher BBB permeability than NAC.…”

Continuous monitoring reveals protective effects ofN-acetylcysteine amide on an isogenic microphysiological model of the neurovascular unit

“…While the literature does not provide prior examples for NACA, one study with an epithelial Caco-2 barrier model has reported P app for NAC below their assay detection limit (~5-10 nm s -1 ). [51] Compared to hiBMEC, Caco-2 are typically leakier (e.g., 13 versus <2.5 nm s -1 for sodium fluorescein). [9,52] Taken together, this may indicate that indeed NACA features higher BBB permeability than NAC.…”

“…While the literature does not provide prior examples for NACA, one study with an epithelial Caco-2 barrier model has reported Papp for NAC below their assay detection limit (~5−10 nm s −1 ). [51] Compared to hiBMEC, Caco-2 are typically leakier (e.g., 13…”

Asam Posfat (H3PO4): Ionic Transformation of Phosphoric Acid in Aqueous Solution

“…Konduktivitas listrik pada larutan H3PO4 (26)(27)(28)(29)(30)(31)(32)(33)(34)(35) Grafik 1. Konduktivitas Listrik pada Larutan H3PO4 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) Konduktivitas hidrolik Parameter atau ukuran yang dapat menggambarkan kemampuan tanah dalam melewatkan air disebut sebagai konduktivitas hidrolik (Hydraulic Conductivity) (1,2,(62)(63)(64)(65)(66)(67)(68)(69)(70)(71) . Tingkat kemampuan tanah untuk melewatkan air sangat dipengaruhi oleh kadar air tanah.…”