Novel carbocyclic nucleoside analogs suppress glomerular mesangial cells proliferation and matrix protein accumulation through ROS-dependent mechanism in the diabetic milieu. II. Acylhydrazone-functionalized pyrimidines

Bouhadir, Kamal H.; Koubeissi, Ali; Mohsen, Fatima A.; El-Harakeh, Mira Diab; Cheaib, Rouba; Younes, J.; Azzi, Georges El; Eid, Assaad A.

doi:10.1016/j.bmcl.2015.12.042

Cited by 6 publications

(2 citation statements)

References 35 publications

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“…In addition to maintaining the capillary loop, MCs are also involved in mediating the apoptotic activity of multiple cells [33]. Nephrons are conventionally believed to be the units that comprise the structural and functional basis of the kidney, and decreased nephrons can cause proteinuria by damaging glomerular filtration and reabsorption by renal tubules [34]. As DN progresses into the mid-or late-stage, cellular apoptosis increases in the glomerulus, leading to a destructive effect on glomerular filtration, which further aggravates the albuminuria [35].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: XBP1 inhibits mesangial cell apoptosis in response to oxidative stress via the PTEN/AKT pathway in diabetic nephropathy

Wang

Qiu

et al. 2019

FEBS Open Bio

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Diabetic nephropathy ( DN ) is a complication of diabetes mellitus ( DM ) that frequently results in renal disease, and is characterized by a variety of symptoms, including albuminuria. It has been shown that apoptosis of glomerular mesangial cells ( MC s) can aggravate albuminuria and contribute to the development of diabetic glomerulosclerosis. Hence, determination of the mechanisms leading to MC apoptosis may help us gain insights into the pathogenesis of DN . As our understanding of the role of high glucose ( HG ) in MC apoptosis remains elusive, we explored the interplay between X‐box binding protein 1 ( XBP 1) and MC apoptosis in this study. XBP 1 was observed to be downregulated both in vivo and in vitro . Treatment of XBP 1‐overexpressing cells with HG resulted in a decrease of reactive oxygen species ( ROS ) and a suppression of cell apoptosis, concomitant with decreases in cleaved caspase‐3 and Bax. Subsequent analyses demonstrated that XBP 1 overexpression inhibited the expression of phosphatase and tensin homolog deleted on chromosome ten ( PTEN ) and enhanced the activation of AKT in MC s exposed to HG . In addition, XBP 1‐induced injuries in MC were reversed by overexpression of PTEN , and XBP 1 inhibited apoptosis, which was mediated by the activated PTEN / AKT signaling pathway. Thus, our data indicate that XBP 1 can activate the PTEN / AKT signaling pathway, thereby alleviating oxidative stress caused by HG or MC apoptosis. These findings suggest that XBP 1 may have potential in the development of treatment methods for DN .

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Section: Discussionmentioning

confidence: 99%

RETRACTED: XBP1 inhibits mesangial cell apoptosis in response to oxidative stress via the PTEN/AKT pathway in diabetic nephropathy

Wang

Qiu

et al. 2019

FEBS Open Bio

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“…Uracil compounds are promising structures in the field of drug discovery ( Bouhadir et al, 2016 ; Putz and Dudas, 2013 ). Uracils substituted in position five stand out in bioactivity ( Gimadieva et al, 2015 ), with various biological activities including antiviral properties ( Palasz and Ciez, 2015 ), anticancer, cytotoxic ( Tanase et al, 2015 ; Krutikov and Erkin, 2009 ), antimycobacterial ( Isobe et al, 2003 ; Baraldi et al, 2002 ), and antitumor ( Seferoglu and Ertan, 2008 ), to antibacterial ( Lee et al, 1997 ).…”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of new thiazolidinone/uracil derivatives as antiproliferative agents targeting EGFR and/or BRAFV600E

et al. 2022

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Thiourea derivatives of uracil were efficiently synthesized via the reaction of 5-aminouracil with isothiocyanates. Then, we prepared uracil-containing thiazoles via condensation of thioureas with diethyl/dimethyl acetylenedicarboxylates. The structures of the products were confirmed by a combination of spectral techniques including infra-red (IR), nuclear magnetic resonance (NMR), mass spectrometry (MS) and elemental analyses. A rationale for the formation of the products is presented. The newly synthesized compounds were evaluated for their in vitro antiproliferative activity against four cancer cell lines. The compounds tested showed promising antiproliferative activity, with GI50 values ranging from 1.10 µM to 10.00 µM. Compounds 3c, 5b, 5c, 5h, 5i, and 5j were the most potent derivatives, with GI50 values ranging from 1.10 µM to 1.80 µM. Compound 5b showed potent inhibitory activity against EGFR and BRAFV600E with IC50 of 91 ± 07 and 93 ± 08 nM, respectively, indicating that this compound could serve as a dual inhibitor of EGFR and BRAFV600E with promising antiproliferative properties. Docking computations revealed the great potency of compounds 5b and 5j towards EGFR and BRAFV600E with docking scores of −8.3 and −9.7 kcal/mol and −8.2 and −9.3 kcal/mol, respectively.

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Spectroscopic Evaluation of Novel Adenine/Thymine-Conjugated Naphthalenediimides: Preference of Adenine-Adenine over Thymine-Thymine Intermolecular Hydrogen Bonding in Adenine- and Thymine-Functionalized Naphthalenediimides

et al. 2019

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Novel carbocyclic nucleoside analogs suppress glomerular mesangial cells proliferation and matrix protein accumulation through ROS-dependent mechanism in the diabetic milieu. II. Acylhydrazone-functionalized pyrimidines

Cited by 6 publications

References 35 publications

RETRACTED: XBP1 inhibits mesangial cell apoptosis in response to oxidative stress via the PTEN/AKT pathway in diabetic nephropathy

RETRACTED: XBP1 inhibits mesangial cell apoptosis in response to oxidative stress via the PTEN/AKT pathway in diabetic nephropathy

Design and synthesis of new thiazolidinone/uracil derivatives as antiproliferative agents targeting EGFR and/or BRAFV600E

Spectroscopic Evaluation of Novel Adenine/Thymine-Conjugated Naphthalenediimides: Preference of Adenine-Adenine over Thymine-Thymine Intermolecular Hydrogen Bonding in Adenine- and Thymine-Functionalized Naphthalenediimides

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