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Synthesis and cardiomyocyte protection activity of crocetin diamide derivatives.
Fitoterapia 2017 September
A series of novel diamide derivatives (2-8) of crocetin (1) were synthesized and evaluated for their cardioprotective activity in vitro. Using well-established model of hypoxia-induced injury in H9c2 cells, we investigated the effects of 9 compounds and positive drug nicorandil on cellular cytotoxicity by MTT assay, mitochondrial viable staining, LDH activity and mitochondrial membrane potential (MMP). Among the new derivatives, compounds 3 and 4 with good liposolubility showed significantly potent activity than crocetin (1) against hypoxia-induced cytotoxicity. Further mechanisms studies indicated that the cardioprotective effect of compounds 3 and 4 was due to these abilities by decreasing LDH release, preserving mitochondrial viabilities and reducing oxidative stress-induced depolarization of MMP. Our results demonstrated that compounds 3 and 4 as a new class of crocetin diamide derivatives could be developed as potential agents in our further drug development studies for ischemic heart disease.
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