A quinazoline-derivative compound with PARP inhibitory effect suppresses hypertension-induced vascular alterations in spontaneously hypertensive rats

Magyar, Klara; Deres, László; Erős, Krisztián; Bruszt, Kitti; Seress, László; Hamar, J.; Hideg, Kálmán; Balogh, András; Gallyas, Ferenc; Sümegi, Balázs; Tóth, Kálmán; Halmosi, Róbert

doi:10.1016/j.bbadis.2014.03.008

Cited by 26 publications

(28 citation statements)

References 64 publications

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“…Further, TNF-α can activate the expression of NF-kappaB and increase its activity [73]. It was previously demonstrated that in both asthma and hypertension, the activity of NF-kappaB is enhanced [74][75][76][77]. Figure 2 illustrates that, in turn, NF-kappaB is able to reduce the level of expression of the apolipoprotein A1 (apoA-1) gene [78].…”

Section: Associative Gene Network Of Asthma and Hypertensionmentioning

confidence: 96%

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

et al. 2018

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Background: Hypertension and bronchial asthma are a major issue for people's health. As of 2014, approximately one billion adults, or~22% of the world population, have had hypertension. As of 2011, 235-330 million people globally have been affected by asthma and approximately 250,000-345,000 people have died each year from the disease. The development of the effective treatment therapies against these diseases is complicated by their comorbidity features. This is often a major problem in diagnosis and their treatment. Hence, in this study the bioinformatical methodology for the analysis of the comorbidity of these two diseases have been developed. As such, the search for candidate genes related to the comorbid conditions of asthma and hypertension can help in elucidating the molecular mechanisms underlying the comorbid condition of these two diseases, and can also be useful for genotyping and identifying new drug targets. Results: Using ANDSystem, the reconstruction and analysis of gene networks associated with asthma and hypertension was carried out. The gene network of asthma included 755 genes/proteins and 62,603 interactions, while the gene network of hypertension -713 genes/proteins and 45,479 interactions. Two hundred and five genes/proteins and 9638 interactions were shared between asthma and hypertension. An approach for ranking genes implicated in the comorbid condition of two diseases was proposed. The approach is based on nine criteria for ranking genes by their importance, including standard methods of gene prioritization (Endeavor, ToppGene) as well as original criteria that take into account the characteristics of an associative gene network and the presence of known polymorphisms in the analysed genes. According to the proposed approach, the genes IL10, TLR4, and CAT had the highest priority in the development of comorbidity of these two diseases. Additionally, it was revealed that the list of top genes is enriched with apoptotic genes and genes involved in biological processes related to the functioning of central nervous system.

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Section: Associative Gene Network Of Asthma and Hypertensionmentioning

confidence: 96%

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

et al. 2018

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“…It was discovered that within 32 week of experimental duration, SBP of hypertensive (SHR-C, SHR-L) rats was remarkably greater as compared with normotensive (WKY) rats (Magyar et al, 2014) and the detail of the finding is shown in Figure 13. Administering L-2286 was noticed to contribute no significant change to SBP of SHR rats during the 32 week treatment period (Magyar et al, 2014).…”

Section: Antihypertensive Activitymentioning

confidence: 99%

“…The administration of L-2286 in hypertensive animals has been hypothesized to decrease oxidative stress, modulate signaling pathways (PI-3K-Akt, MAP kinases) and attenuate NF-κB activation, thereby reduces the hypertension-induced adverse vascular changes (Magyar et al, 2014). It is well established that PARP inhibitors can prevent oxidative stress induced tissue damage; they can favorably modulate PI-3-kinase/Akt-1 and MAP kinase pathways, and inhibit NF-κB activation (Radnai et al, 2012).…”

Section: Antihypertensive Activitymentioning

confidence: 99%

“…It is well established that PARP inhibitors can prevent oxidative stress induced tissue damage; they can favorably modulate PI-3-kinase/Akt-1 and MAP kinase pathways, and inhibit NF-κB activation (Radnai et al, 2012). Although, PARP inhibition did not have any antihypertensive effect, it enforces salient safeguarding upon process of change of hypertensive heart disorder to heart failure in SHRs (Magyar et al, 2014;Bartha et al, 2009). A series of novel substituted quinazolin-4(3H) -one derivatives, with acute LD50>1000 mg/kg, showed enhanced bioactivity than standard drug prazosin, which plays unique role as anti-hypertensive agent through 1 blocking procedure (Pathak et al, 2014).…”

Section: Antihypertensive Activitymentioning

confidence: 99%

“…A series of novel substituted quinazolin-4(3H) -one derivatives, with acute LD50>1000 mg/kg, showed enhanced bioactivity than standard drug prazosin, which plays unique role as anti-hypertensive agent through 1 blocking procedure (Pathak et al, 2014). The effect of L-2286 on systolic blood pressure (SBP) was investigated by Magyar et al (2014). It was discovered that within 32 week of experimental duration, SBP of hypertensive (SHR-C, SHR-L) rats was remarkably greater as compared with normotensive (WKY) rats (Magyar et al, 2014) and the detail of the finding is shown in Figure 13.…”

Section: Antihypertensive Activitymentioning

confidence: 99%

See 2 more Smart Citations

Quinazoline pharmacophore in therapeutic medicine

Ajani

Aderohunmu

Umeokoro

et al. 2016

Bangladesh J Pharmacol

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This present study comprehensively expatiates the functionalized utilization of quinazoline scaffolds in drug development and furnishes latest updates in pharmacological appositeness of its derivatives in order to reveal novel pathways for therapeutic targets. It traverses numerous biological potentials of quinazoline in the contemporary time to allow researchers' unhindered access to the beneficial role of quinazoline in fighting infectious diseases for future drug discovery. This work provides broad overview of medicinal survey of quinazoline chemistry valuable in the discovery of more efficient clinical trials and to summarize the most promising molecular targets for drug design. Article Info

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Dehydrogenative Coupling for Synthesis of Quinazolin‐4(3H)‐ones via Tandem Reaction using Ruthenium(II)‐Phenyl‐Azo‐Naphthaldoxime: An Experimental and Theoretical Investigation

Halder,

Naskar,

Jana

et al. 2024

Chemistry An Asian Journal

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The bidentate N, N, donor phenyl‐azo‐naphthaldoxime NpLH, 1 was used to synthesize the ruthenium(II) complex trans‐[Ru(NpL)(CO)Cl(PPh3)2], 2. It has been characterized by SCXRD, electrochemical and spectral studies. Computational analysis indicates that the low‐lying p*‐LUMO of the complex has substantial azo‐character of coordinated ligand. This property has been exploited to form an efficient electron transfer pre‐catalyst to effectuate dehydrogenative functionalization of a large number of benzyl alcohols to quinazolin‐4(3H)‐ones via condensation with diverse o‐amino benzamides as well as N‐substituted benzamides under aerobic conditions (57 entries). A reaction mechanism has been projected via isolation of intermediates and certain control experiments. Furthermore, it has been substantiated by theoretical scrutiny using density functional theory (DFT) calculation. The catalytic cycle involves stepwise hydrogen atom transfer (HAT) from benzyl alcohols to the Nazo atoms of the coordinated ligand with subsequent removal of the H‐atoms from the Nazo atoms to regenerate the active catalyst.

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A quinazoline-derivative compound with PARP inhibitory effect suppresses hypertension-induced vascular alterations in spontaneously hypertensive rats

Cited by 26 publications

References 64 publications

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

Quinazoline pharmacophore in therapeutic medicine

Dehydrogenative Coupling for Synthesis of Quinazolin‐4(3H)‐ones via Tandem Reaction using Ruthenium(II)‐Phenyl‐Azo‐Naphthaldoxime: An Experimental and Theoretical Investigation

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