scholarly journals Synthesis and Antineoplastic Evaluation of Mitochondrial Complex II (Succinate Dehydrogenase) Inhibitors Derived from Atpenin A5

ChemMedChem ◽  
2017 ◽  
Vol 12 (13) ◽  
pp. 1033-1044 ◽  
Author(s):  
Hezhen Wang ◽  
Bader Huwaimel ◽  
Kshitij Verma ◽  
James Miller ◽  
Todd M. Germain ◽  
...  
2012 ◽  
Vol 19 (6) ◽  
pp. C33-C40 ◽  
Author(s):  
Paraskevi Xekouki ◽  
Constantine A Stratakis

Succinate dehydrogenase (SDH) or mitochondrial complex II is a multimeric enzyme that is bound to the inner membrane of mitochondria and has a dual role as it serves both as a critical step of the tricarboxylic acid or Krebs cycle and as a member of the respiratory chain that transfers electrons directly to the ubiquinone pool. Mutations in SDH subunits have been implicated in the formation of familial paragangliomas (PGLs) and/or pheochromocytomas (PHEOs) and in Carney–Stratakis syndrome. More recently, SDH defects were associated with predisposition to a Cowden disease phenotype, renal, and thyroid cancer. We recently described a kindred with the coexistence of familial PGLs and an aggressive GH-secreting pituitary adenoma, harboring anSDHDmutation. The pituitary tumor showed loss of heterozygosity at theSDHDlocus, indicating the possibility thatSDHD's loss was causatively linked to the development of the neoplasm. In total, 29 cases of pituitary adenomas presenting in association with PHEOs and/or extra-adrenal PGLs have been reported in the literature since 1952. Although a number of other genetic defects are possible in these cases, we speculate that the association of PHEOs and/or PGLs with pituitary tumors is a new syndromic association and a novel phenotype for SDH defects.


Plant Science ◽  
2020 ◽  
Vol 294 ◽  
pp. 110458 ◽  
Author(s):  
Jin Seok Shin ◽  
Won Mi So ◽  
Soo Youn Kim ◽  
Minsoo Noh ◽  
Sujin Hyoung ◽  
...  

2012 ◽  
Vol 73 (3) ◽  
pp. 429-441 ◽  
Author(s):  
Shaobai Huang ◽  
Nicolas L. Taylor ◽  
Elke Ströher ◽  
Ricarda Fenske ◽  
A. Harvey Millar

2015 ◽  
Vol 208 (3) ◽  
pp. 776-789 ◽  
Author(s):  
Douglas Jardim-Messeder ◽  
Andréia Caverzan ◽  
Rafael Rauber ◽  
Eduardo de Souza Ferreira ◽  
Márcia Margis-Pinheiro ◽  
...  

2015 ◽  
Vol 22 (4) ◽  
pp. T71-T82 ◽  
Author(s):  
Bora E Baysal ◽  
Eamonn R Maher

Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine neoplasms that derive from small paraganglionic tissues which are located from skull base to the pelvic floor. Genetic predisposition plays an important role in development of PPGLs. Since the discovery of first mutations in the succinate dehydrogenase D (SDHD) gene, which encodes the smallest subunit of mitochondrial complex II (SDH), genetic studies have revealed a major role for mutations in SDH subunit genes, primarily in SDHB and SDHD, in predisposition to both familial and non-familial PPGLs. SDH-mutated PPGLs show robust expression of hypoxia induced genes, and genomic and histone hypermethylation. These effects occur in part through succinate-mediated inhibition of α-ketoglutarate-dependent dioxygenases. However, details of mechanisms by which SDH mutations activate hypoxic pathways and trigger subsequent neoplastic transformation remain poorly understood. Here, we present a brief review of the genetic and mechanistic aspects of SDH-mutated PPGLs.


2021 ◽  
Vol 69 (13) ◽  
pp. 3965-3971
Author(s):  
Ge Wei ◽  
Ming-Wei Huang ◽  
Wen-Jie Wang ◽  
Yuan Wu ◽  
Shu-Fen Mei ◽  
...  

Author(s):  
Thomas Assinger ◽  
Stefano F. F. Torriani ◽  
Salvatore Accardo ◽  
James Fountaine ◽  
Siegrid Steinkellner

AbstractRamularia collo-cygni B. Sutton and J.M. Waller is a major disease in Austrian barley-growing regions. To date, fungicide application is the most effective method to manage the disease; however, fungicide resistance to demethylation and succinate dehydrogenase inhibitors has developed over the last few years. In the growing seasons 2016/2017 and 2017/2018, field trials were carried out to analyze the efficiency of fungicide strategies based on different fungicide classes. Disease development, growth parameters and monitoring of CYP51 and sdh mutations were determined. Fungicide treatments resulted in higher disease control, green leaf area and grain yield. In Austrian R. collo-cygni field populations, the frequency of the mutations CYP51-I325T and CYP51-I328L was low to moderate. Frequency of mutations sdhC-H146R and sdhC-H153R was low. Frequencies of CYP51-I325T and -I328L were similar and increased following DMI application. Frequency of sdhC-H146R was higher compared to sdhC-H153R. The SDHI benzovindiflupyr showed a higher selection rate for sdh mutations compared to bixafen. These sdh mutations were not selected if chlorothalonil was used as mixing partner, leading to a stable composition of sdh resistance alleles over the last two years. Chlorothalonil was proven to be an effective tool for anti-resistance strategies. Currently, SDHIs and DMIs are the backbone of Ramularia leaf spot control in Austria; however, the level of resistance is likely to increase in absence of suitable anti-resistance strategies and following the ban of chlorothalonil.


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