Effect on mitochondrial outer membrane of six selected synthetic cyclic chalcone analogues, E-2-arylmethylene-1-tetralones (2) and E-2-arylmethylene-1-benzosuberones (3), were investigated by fluorescence spectroscopy. The selected compounds represent derivatives with different degree of cytotoxicity against murine and human cancer lines. Excitation and emission fluorescence spectra of the cyclic chalcone analogues 2 and 3 were recorded in respiration medium containing 1 mM succinate. It was found that the ring size as well as the nature and location of the aromatic substituents have significant effect on fluorescence of the compounds. Interaction of subtoxic concentration of compounds 2 and 3 with the outer mitochondrial membrane was investigated by recording their fluorescence polarization in the presence of rat liver mitochondria. The most cytotoxic E-2-(4'-methoxybenzylidene)-1-benzosuberone (3b) was found to display a continuous increase of fluorescence polarization signal in the presence of mitochondria--a different pattern of interaction with the mitochondrial outer membrane from that observed for rest of the investigated compounds.
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http://dx.doi.org/10.1016/j.jbbm.2004.04.010 | DOI Listing |
Liver Int
January 2025
Liver Center, Digestive Diseases Section, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Background & Aims: Approximately 40% of patients with Primary Biliary Cholangitis (PBC) show incomplete response to ursodeoxycholic acid, thus needing second-line treatment to prevent disease progression. As no head-to-head comparison study is available, we used a network meta-analysis (NMA) to compare efficacy and safety of available second-line therapies.
Methods: We performed a systematic literature review including randomised, placebo-controlled trials of patients with PBC and incomplete response, or intolerance, to ursodeoxycholic acid, and compared relative risks (RRs) for primary (biochemical response at 52-week) and secondary outcomes [incidence of new-onset pruritus and serious adverse events (SAEs)].
Chem Biodivers
December 2024
Department of Chemistry, Çankırı Karatekin University, Çankırı, Turkey.
In this study, novel thiazole-chalcone analogs were synthesized, and their inhibitory effects on acetylcholinesterase (AChE) were examined. In vitro enzyme activity studies were conducted to calculate IC values, which were found to range between 2.55 and 72.
View Article and Find Full Text PDFImmun Inflamm Dis
December 2024
Department of Geriatric Intensive Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Molecules
November 2024
Institute of Pharmaceutical Chemistry, University of Pécs, H-7624 Pécs, Hungary.
In vitro relative cytotoxicity (IC ()/IC () of ()-3-(4'-methylbenzylidene)-4-chromanone () towards human Molt 4/C8 and CEM T-lymphocytes showed a >50-fold increase in comparison to those of the respective tetralone derivative (). On the other hand, such an increase was not observed in the analogous 4-OCH ( and ) derivatives. In order to study whether thiol reactivity-as a possible basis of the mechanism of action-correlates with the observed cytotoxicities, the kinetics of the non-enzyme catalyzed reactions with reduced glutathione (GSH) and N-acetylcysteine (NAC) of and were investigated.
View Article and Find Full Text PDFJ Org Chem
December 2024
Dipartimento di Chimica e Biologia "A. Zambelli", Università degli Studi di Salerno, 84084 Fisciano, SA, Italy.
Herein we report two processes facilitated by diisopropylethylamine (DIPEA) for the synthesis of novel bridged polycyclic molecule analogues to natural products. The use of 4-bromoisochroman-3-one initiated an autoxidation reaction, followed by a Diels-Alder cycloaddition in the presence of electron-deficient dienophiles. Mechanistic studies revealed isochromane-3,4-dione as a key intermediate, which undergoes in situ dienolization/dearomatization followed by a [4 + 2] cycloaddition.
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