Search

Objective(s): Cisplatin is an effective antineoplastic agent; its clinical utility, however, is limited by a few salient toxic side effects like nephrotoxicity. This study aimed to determine the potential protective effects of tangeretin, a citrus-derived flavonoid, against renal tubular cell injury in cisplatin-induced renal toxicity of rats. Materials and Methods: Tangeretin was injected intraperitoneally at 2.5 and 5 mg/kg doses for 10 days, and a single dose of cisplatin (8 mg/kg) was injected on the 7th day. Tests of kidney function and tubular injury in renal tissues and urine together with oxidative stress and inflammation markers were examined. Results: Tangeretin ameliorated cisplatin-induced elevations in serum creatinine, BUN, and histopathologic changes. It also attenuated kidney oxidative stress elicited by cisplatin as demonstrated by reduced MDA and increased GSH, CAT, and SOD activities, elevated Nrf2 expression and protein levels of its downstream effectors, HO-1 and NQO-1. Tangeretin further alleviated inflammation evoked by cisplatin as indicated by reduced NF-κB p65 subunit phosphorylation with a simultaneous decrement in its downstream effectors IL-1β and TNF-α expression and protein levels. Moreover, it declined caspase-3 protein levels and TUNEL positive cells in the kidneys, the markers of apoptosis and DNA fragmentation, thus improving renal endurance. Additionally, tangeretin mitigated renal levels of KIM-1 and NGAL, as well as urinary cystatin C and β2-microglobulin concentrations, the markers of renal tubular injury. Conclusion: Collectively, these data signify the binary profit of tangeretin: enhancement of renal protective mechanisms against cisplatin and attenuation of renal tubular cell injuries induced by the agent. [ABSTRACT FROM AUTHOR]

Despite being an efficacious anticancer agent, the clinical utility of cisplatin is hindered by its cardinal side effects. This investigation aimed to appraise potential protective impact of dunnione, a natural naphthoquinone pigment with established NQO1 stimulatory effects, on cisplatin nephrotoxicity of rats. Dunnione was administered orally at 10 and 20 mg/kg doses for 4 d and a single injection of cisplatin was delivered at the second day. Renal histopathology, inflammatory/oxidative stress/apoptotic markers, kidney function, and urinary markers of renal injury were assessed. Dunnione repressed cisplatin-induced inflammation in the kidneys as indicated by decreased TNF-α/IL-1β levels, and reduced nuclear phosphorylated NF-κB p65. This agent also obviated cisplatin-invoked oxidative stress as elucidated by decreased MDA/GSH levels and increased SOD/CAT activities. Dunnione, furthermore, improved renal histological deteriorations as well as caspase-3 activities and terminal deoxynucleotidyl transferase (TUNEL) positive cells, the indicators of apoptosis. Moreover, it up-regulated nuclear Nrf2 and cytosolic haeme-oxygenase-1 (HO-1) and NQO1 levels; meanwhile, promoted NAD+/NADH ratios followed by enhancing the activities of Sirt1 and PARP1; and further attenuated nuclear acetylated NF-κB p65. Dunnione additionally declined cisplatin-evoked retrogression in renal function and upraise in urinary markers of glomerular and tubular injury as demonstrated by decreased serum urea and creatinine with simultaneous reductions in urinary excretions of collagen type IV, podocin, cystatin C, and retinol-binding protein (RBP). Altogether, these findings offer dunnione as a potential protective agent against cisplatin-induced nephrotoxicity in rats. [ABSTRACT FROM AUTHOR]

A new approach for the efficient synthesis of imidazo[1,2- a]pyridines is described. The synthesis was carried out via the reaction of functionalized 2-aminopyridine that were formed through a threecomponent reaction and phenacyl bromide derivatives. [ABSTRACT FROM AUTHOR]

Quinolone are a class of potent broad-spectrum antibacterial drugs that target the bacterial type II DNA topoisomerases (DNA gyrase) and topoisomerase IV. In the present study, the synthesis and evaluation of cytotoxicity activity of a new series of N-pipearzinyl quinolones containing N- 2-(furyl-2-yl)-2-(chlorobenzyloxyimino) ethyl moiety (6a-c) have been studied. Preliminary screening showed that one of the new compounds, namely 7-(4-(2- (3-chlorobenzyloxyimino)-2-(furan-2-yl) ethyl) piperazin-1-yl)-1-cyclopropyl- 6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (6b) showed significant cytotoxic activity against human breast tumor cell lines. [ABSTRACT FROM AUTHOR]

Nano magnetic Fe3O4 based vanadic acid [MNPs@VO(OH)2] (average diameter 20-26 nm) has been synthesized by grafting VOCl3 on the Fe3O4 surface nanoparticles as a retrievable supporter to produce novel heterogeneous reusable solid acid with dual ability (Bronsted and Lewis acid) followed by stirring in the air. The resultant material was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) analysis and energy-dispersive X-ray spectroscopy (EDX). Significantly, the as-prepared [MNPs@VO(OH)2] exhibits a high catalytic activity in the synthesis of 4,4'-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols). Additionally, the newly synthesized heterogeneous solid acid catalyst can be reused for several times without apparent loss of its catalytic activity. [ABSTRACT FROM AUTHOR]

Abstract: In this work, the efficiency, generality and applicability of novel Brønsted acidic ionic liquid triethylamine-bonded sulfonic acid {[Et3N–SO3H]Cl, N,N-diethyl-N-sulfoethanammonium chloride} as homogeneous and green catalyst for organic transformations under various conditions are studied. Herein, the following one-pot multi-component reactions in the presence of {[Et3N–SO3H]Cl are investigated: (i) the synthesis of β-acetamido ketones from acetophenones, aldehydes, acetonitrile and acetyl chloride in solution and under extremely mild conditions (room temperature), (ii) the preparation of 1,8-dioxo-octahydroxanthenes from dimedone (5,5-dimethyl-1,3-cyclohexanedione) (2 equiv.) and aldehydes (1 equiv.) under solvent-free conditions at moderate temperature (80°C), and (iii) the synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes from β-naphthol (2 equiv.) and aldehydes (1 equiv.) in harsh conditions (120°C) in the absence of solvent. High yields, relatively short reaction times, efficiency, generality, clean process, simple methodology, low cost, easy work-up, ease of preparation and regeneration of the catalyst and green conditions (in the synthesis of the xanthene derivatives) are advantages of the application of [Et3N–SO3H]Cl as catalyst in the above organic reactions. This work is the first report of the ionic liquid. [Copyright &y& Elsevier]

Brønstedacidic ionic liquid 3-methyl-1-sulphonic acid imidazoliumchloride {[Msim]Cl} is utilized as a highly efficient, inexpensive, mild and green catalyst for the synthesis of β-acetamido ketones by the one-pot multi-component coupling between acetophenones, arylaldehydes, acetonitrile and acetyl chloride at room temperature. Under these conditions, the title compounds are produced in high to excellent yields and in relatively short reaction times. In addition, this method is superior to reported methods, for the synthesis of β-acetamido ketones and is applicable for the synthesis of tris(β-acetamido ketone). [ABSTRACT FROM AUTHOR]

Despite being an efficacious anticancer agent, the clinical utility of cisplatin is hindered by its cardinal side effects. This investigation aimed to appraise potential protective impact of dunnione, a natural naphthoquinone pigment with established NQO1 stimulatory effects, on cisplatin nephrotoxicity of rats. Dunnione was administered orally at 10 and 20 mg/kg doses for 4 d and a single injection of cisplatin was delivered at the second day. Renal histopathology, inflammatory/oxidative stress/apoptotic markers, kidney function, and urinary markers of renal injury were assessed. Dunnione repressed cisplatin-induced inflammation in the kidneys as indicated by decreased TNF-α/IL-1β levels, and reduced nuclear phosphorylated NF-κB p65. This agent also obviated cisplatin-invoked oxidative stress as elucidated by decreased MDA/GSH levels and increased SOD/CAT activities. Dunnione, furthermore, improved renal histological deteriorations as well as caspase-3 activities and terminal deoxynucleotidyl transferase (TUNEL) positive cells, the indicators of apoptosis. Moreover, it up-regulated nuclear Nrf2 and cytosolic haeme-oxygenase-1 (HO-1) and NQO1 levels; meanwhile, promoted NAD + /NADH ratios followed by enhancing the activities of Sirt1 and PARP1; and further attenuated nuclear acetylated NF-κB p65. Dunnione additionally declined cisplatin-evoked retrogression in renal function and upraise in urinary markers of glomerular and tubular injury as demonstrated by decreased serum urea and creatinine with simultaneous reductions in urinary excretions of collagen type IV, podocin, cystatin C, and retinol-binding protein (RBP). Altogether, these findings offer dunnione as a potential protective agent against cisplatin-induced nephrotoxicity in rats.