Chromone-3-aldehyde derivatives – sirtuin 2 inhibitors for correction of muscular dysfunction

Abstract

The aim of the study was to evaluate experimentally, the myoprotective effect of new chromone-3-aldehyde derivatives in conditions of muscular dysfunction and to establish a potential mechanism of myoprotective activity – the blockade of the function of sirutin 2. Materials and methods. The effect of new chromone-3-aldehyde derivatives on the development of muscular dysfunction under the conditions of an electromiostimulation test, was studied. The degree of muscle fatigue was evaluated in the «grip-strength» and through test biochemical assays (determination of the activity of lactate dehydrogenase, creatine kinase, concentration of lactic and pyruvic acids, creatinine, myoglobin, and total protein) to determine the possible mechanism of action of the test compounds (5 new derivatives of chromone-3-aldehyde) and their effect on the function of sirtuin 2 was evaluated. Results. The study showed that chromone-3-aldehyde derivatives have a pronounced myoprotective effect associated with low toxicity (class 5 toxicity according to the GHS classification), which was confirmed by the results of the «grip-strength» test and biochemical tests data. Test compounds under the X3AC1, X3AOAC and X3AN codes evince sirtuin 2 inhibitory activity, which was reflected in a decrease in its concentration by 63.6% (p <0.05); 130.2% (p <0.05) and 218.8% (p <0.05). Conclusion. The study showed that chromone-3-aldehyde derivatives are promising subjects for further study with the goal of creating a drug with a high myoprotective effect and an optimal safety profile.

The cardioprotective effect of 3-formylchromone derivatives. Focus on changes in the functional activity of mitochondria

“…клиническая фармакология пероксид-радикала как в IFM, так и в SSM субпопуляциях, что может быть связано с разобщающим действием данных препаратов на митохондриальный метаболизм. Регуляторный потенциал производных 3-формилхромона в отношении митохондриального биогенеза может быть опосредован влиянием на белки семейства сиртуинов [17], отвечающих практически за все аспекты функциональной активности митохондрий, включая процессы аутофагии, окислительного метаболизма и синтеза органелл de novo [18].…”

Usporedba protutumorske aktivnosti liganada iz skupine benzo/hidrokispirona i bakrova(II) kompleksa s maltolom na 2D staničnim modelima in vitro

“…For example, the compound 4'-methoxy-2-styrylchromone showed cell proliferation activity of 70 % in HeLa cells (human cervical tumour), and 25 % in CHO (Chinese hamster ovary cells). 4 Chromone derivatives bearing different dithiocarbamate (234-237) 5 or styryl (238) 6,7 groups have emerged as promising candidates due to their high efficacy and broad spectrum against HCCLM-7, HeLa, MDA-MB-435S, SW-480, Hep-2, MCF-7 (breast adenocarcinoma), and NCl-H460 (non-small cell lung cancer). Further analysis of flow-activated cell sorting revealed that these compounds arrested the cell cycle of SW-480 and MDA-MB -435S in a dose-dependent manner at G2/M phase, and could have an apoptosis-inducing effect on these tumour cell lines.…”

“…[3][4] Various in vitro, in vivo, and clinical studies have demonstrated the role of chromones in alleviating allergies, reducing oxidative damage, inhibiting cancer, infections and inflammation, and treating neurological and psychiatric disorders. [5][6][7] Of all the ligands used in this study, maltol is the best known. Nowadays, compounds of maltol and some transition metals such as vanadium are known to have excellent insulinomimetic properties, while their antitumour properties are almost unknown.…”