Novel iodinated quinazolinones bearing sulfonamide as new scaffold targeting radiation induced oxidative stress

Soliman, Aiten M.; Mekkawy, Mai H; Karam, Heba M.; Higgins, Maureen; Dinkova‐Kostova, Albena T.; Ghorab, Mostafa M.

doi:10.1016/j.bmcl.2021.128002

Cited by 7 publications

(8 citation statements)

References 65 publications

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“…MDA is one of the paramount end-products of peroxidation of polyunsaturated fatty acids and is commonly used to estimate oxidative stress. 41,71 In the present study, the MDA level in irradiated groups was significantly lower than the non-irradiated EST group. while the levels of MDA and ROS were found to be increased in the tumor tissues of EST bearing mice upon treatment with either BL alone or combined with IRR, in comparison with both untreated and irradiated EST bearing group.…”

Section: Discussioncontrasting

confidence: 40%

Radiosensitizing Effect of Bromelain Using Tumor Mice Model via Ki-67 and PARP-1 Inhibition

et al. 2021

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Recent reports have shown that bromelain (BL), a pineapple extract, acts as an adjuvant therapy in cancer treatment and prevention of carcinogenesis. The present study was designed to investigate the possible mechanisms by which BL could radiosensitize tumor cells in vitro and in a mouse tumor model. BL has shown a significant reduction in the viability of the radioresistant human breast carcinoma (MCF-7) cell line using cell proliferation assay. The in vivo study was designed using the Ehrlich model in female albino mice, treated with BL (6 mg/kg b. wt., intraperitoneal, once daily for 10 days) 1 hour before exposure to a fractionated dose of gamma radiation (5 Gy, 1 Gy for 5 subsequent days). The radiosensitizing effect of BL was evident in terms of a significant reduction in tumor volume, poly ADP ribose polymerase-1 (PARP-1), the proliferation marker Ki-67 and nuclear factor kappa activated B cells (NF-κB) with a significant elevation in the reactive oxygen species (ROS) content and lipid peroxidation (LPO) in tumor cells. The present findings offer a novel insight into the radiosensitizing effect of BL and its potential application in the radiotherapy course.

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Section: Discussioncontrasting

confidence: 40%

Radiosensitizing Effect of Bromelain Using Tumor Mice Model via Ki-67 and PARP-1 Inhibition

et al. 2021

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“…1 ) 39 . The antioxidant activity was also reported for structurally diverse quinazolines such as 2-((4-oxo-3-(4-sulfamoyl-phenyl)-3,4-dihydro-quinazolin-2-yl)thio)- N -(pyrazin-2-yl)-acetamide ( I ) 40 , the 2-(chloromethyl)-3-(4-methyl-6-oxo-5-(( E )-phenyldiazenyl)-2-thioxo-5,6-dihydropyrimidine-1(2 H )-yl)quinazoline-4(3 H )-ones ( II ) 41 , and the iodinated quinazolinone bearing a benzensulfonamide moiety ( III ) 42 (Fig. 1 ).…”

Section: Introductionmentioning

confidence: 99%

Novel iodoquinazolinones bearing sulfonamide moiety as potential antioxidants and neuroprotectors

Soliman,

Ghorab,

Lotfy

et al. 2023

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In a search for new antioxidants, a set of new iodoquinazolinone derivatives bearing benzenesulfonamide moiety and variable acetamide pharmacophores 5–17 were designed and synthesized. The structures of the synthesized compounds were confirmed based on spectral data. Compounds 5–17 were screened using in vitro assay for their antioxidant potential and acetylcholinesterase (AChE) inhibitory activity. The 2-(6-iodo-4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydroquinazolin-2-ylthio)-N-(pyrazin-2-yl) acetamide 14 was the most active scaffold with potent AChE inhibitory activity. Compound 14 showed relative safety with a median lethal dose of 300 mg/kg (LD50 = 300 mg/kg), in an acute toxicity study. The possible antioxidant and neuroprotective activities of 14 were evaluated in irradiated mice. Compound 14 possessed in vivo AChE inhibitory activity and was able to modify the brain neurotransmitters. It was able to cause mitigation of gamma radiation-induced oxidative stress verified by the decline in Myeloperoxidase (MPO) and increase of glutathione (GSH) levels. Also, 14 restored the alterations in behavioral tests. Molecular docking of 14 was performed inside MPO and AChE active sites and showed the same binding interactions as that of the co-crystallized ligands considering the binding possibilities and energy scores. These findings would support that 14 could be considered a promising antioxidant with a neuromodulatory effect.

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“…Novel iodinated quinazolinones bearing sulfonamide were synthesized. Among them there is a compound that acts as a direct antioxidant by scavenging reactive oxygen species and inhibiting radiation-induced oxidative stress [10]. 3-Aryl-8-methylquinazolin-4(3H)-ones have promising properties for drug development against keratitis and brain infection causing free-living amoeba, A.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and evaluation of cerebroprotective activity of novel 6,7-dimethoxyquinazolin-4(3H)-one derivatives containing residues of amino acids and dipeptides

2022

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Neurodegenerative processes of the central nervous system are an important socially significant problem of modern society. They cause many diseases, such as Alzheimer's disease and cerebral ischemia, which significantly reduce the quality of human life and can lead to disability or death. The aim of this study was to synthesize novel 6,7-dimethoxyquinazolin-4(3H)-one derivatives with the remains of neuroactive amino acids and dipeptides in order to investigate their cerebroprotective properties. As a result of the study, 13 novel 6,7-dimetho-xyquinazolin-4(3H)-one derivatives were synthesized. Cerebral ischemia in rats was reproduced by irreversible right-sided occlusion of the middle cerebral artery using the Tamura method, and the area of brain necrosis was evaluated. Cognitive functions were evaluated in the Y-maze test. Among the studied quinazolinone derivatives, compounds 3i, 3j and 3k have the most pronounced cerebrotropic activity, which is not inferior to ethylmethylhydroxypyridine succinate in terms of pharmacological activity, making them promising objects for further research.

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Novel iodinated quinazolinones bearing sulfonamide as new scaffold targeting radiation induced oxidative stress

Cited by 7 publications

References 65 publications

Radiosensitizing Effect of Bromelain Using Tumor Mice Model via Ki-67 and PARP-1 Inhibition

Radiosensitizing Effect of Bromelain Using Tumor Mice Model via Ki-67 and PARP-1 Inhibition

Novel iodoquinazolinones bearing sulfonamide moiety as potential antioxidants and neuroprotectors

Synthesis and evaluation of cerebroprotective activity of novel 6,7-dimethoxyquinazolin-4(3H)-one derivatives containing residues of amino acids and dipeptides

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