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1,3,8-Triazaspiro[4.5]decane Derivatives Inhibit Permeability Transition Pores through a F-ATP Synthase c Subunit Glu-Independent Mechanism That Prevents Oligomycin A-Related Side Effects.
Int J Mol Sci
March 2023
Maria Cecilia Hospital, GVM Care and Research, 48033 Cotignola, Italy.
Permeability transition pore (PTP) molecular composition and activity modulation have been a matter of research for several years, especially due to their importance in ischemia reperfusion injury (IRI). Notably, c subunit of ATP synthase (Csub) has been identified as one of the PTP-forming proteins and as a target for cardioprotection. Oligomycin A is a well-known Csub interactor that has been chemically modified in-depth for proposed new pharmacological approaches against cardiac reperfusion injury.
View Article and Find Full Text PDFSynthesis and evaluation of isoprenylation-resveratrol dimer derivatives against Alzheimer's disease.
Eur J Med Chem
February 2019
Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:
A series of resveratrol dimer derivatives against Alzheimer's disease (AD) was obtained by structural modification and transformation using resveratrol as substrate. Biological analysis revealed that these derivatives had moderate inhibitory activity against human monoamine oxidase B (hMAO-B). In particular, 3 and 7 showed the better inhibitory activity for hMAO-B (IC = 3.
View Article and Find Full Text PDFMitochondrial Genome Variation Affects Multiple Respiration and Nonrespiration Phenotypes in .
Genetics
February 2019
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710
Mitochondrial genome variation and its effects on phenotypes have been widely analyzed in higher eukaryotes but less so in the model eukaryote Here, we describe mitochondrial genome variation in 96 diverse strains and assess associations between mitochondrial genotype and phenotypes as well as nuclear-mitochondrial epistasis. We associate sensitivity to the ATP synthase inhibitor oligomycin with SNPs in the mitochondrially encoded gene. We describe the use of iso-nuclear F1 pairs, the mitochondrial genome equivalent of reciprocal hemizygosity analysis, to identify and analyze mitochondrial genotype-dependent phenotypes.
View Article and Find Full Text PDFRational Design and Multibiological Profiling of Novel Donepezil-Trolox Hybrids against Alzheimer's Disease, with Cholinergic, Antioxidant, Neuroprotective, and Cognition Enhancing Properties.
ACS Chem Neurosci
November 2017
Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
A novel series of donepezil-trolox hybrids were designed, synthesized, and evaluated as multifunctional ligands against Alzheimer's disease (AD). Biological assays showed that these derivatives possessed moderate to good inhibitory activities against acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B) as well as remarkable antioxidant effects. The optimal compound 6d exhibited balanced functions with good inhibition against hAChE (IC = 0.
View Article and Find Full Text PDFMethylene blue stimulates substrate-level phosphorylation catalysed by succinyl-CoA ligase in the citric acid cycle.
Neuropharmacology
September 2017
Department of Medical Biochemistry, MTA-SE Laboratory for Neurobiochemistry, Semmelweis University, 37-47 Tuzolto St., Budapest, 1094, Hungary. Electronic address:
Methylene blue (MB), a potential neuroprotective agent, is efficient in various neurodegenerative disease models. Beneficial effects of MB have been attributed to improvements in mitochondrial functions. Substrate-level phosphorylation (SLP) results in the production of ATP independent from the ATP synthase (ATP-ase).
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