Synthesis and anticancer effects of α-lipoic ester of alloxanthoxyletin

Abstract

Upon analyzing the structure-activity relationship, it was found that coumarin-based derivatives exerted cytotoxic and antitumor activity. In the present study a new ester of α-lipoic acid and derivative of alloxanthoxyletin (LAA) was synthesized and evaluated for its anticancer activity. The structure of this new compound was confirmed by 1 H NMR, 13 C NMR, and HRMS spectroscopic analyses. Both, the cytotoxicity and the migration tests showed that human melanoma cells (HTB-140) and human lung cancer cells (A549) were more sensitive to LAA exposure than human normal keratinocytes (HaCaT). Moreover, LAA induced significant HTB-140 and A549 apoptosis, as evidenced by V-FITC/7-AAD flow cytometry analysis. Preincubation of the HTB-140 and A549 cells with LAA increased a sensitivity of tumor cells to a druginduced cell death. Significantly lower expression of IL-6 mRNA was observed in A549 and HTB-140 cells which were preincubated with LAA and then treated with doxorubicin as compared to the cells pre-incubated with LAA and then treated with cisplatin. The results suggest that the newly synthetized LAA is compound with anticancer activity promising for potential applications, but further studies are needed to gain more insight into the mechanism of action of tested derivative.

In Silico and In Vitro Evaluation of the Antifungal Activity of a New Chromone Derivative against Candida spp.

“…The coumarin derivatives showed moderate cytotoxicity at 100 μM) [ 60 ]. Other studies have also reported low cytotoxicity of coumarin derivatives, with an IC50 expression of 55.5 μM on human keratinocyte [ 61 ], suggesting the need for further cytotoxic analyses with (E)-benzylidene-chroman-4-one as the results are promising compared to similar compounds. Therefore, conducting in vivo studies is advised to assess additional parameters of toxicity.…”