Title: Flavonoids-Substitution status to predict anticancer activity in selected human skin cancers

Abstract

Skin cancer affects millions of people every year. The growing number of skin cancer cases in recent decades and especially the most common melanoma, requires the search for new methods of treatment. An important area of studies is the search for therapeutic agents among natural products that could be a substrate for the production of more effective semi-synthetic drugs. Both in vitro and in vivo studies have shown that flavonoids have the ability to prevent carcinogenesis and inhibit the growth of cancer cells. In this study, we used bioinformatics tool to search for flavonoid compounds with potential anticancer activity in extensive in vitro biological studies. In this regard, we tested the activity of 36 structurally diverse flavonoids and cis-platinum as a reference drug against the SCC-25 cell line, as well as two melanoma cell lines, C32 and A375. Initial screening for antitumor activity was performed with the MTT and NRU assays (after 24 h, 48 h and 72 h incubation). In the MTT assay, the most active (indicated as IC50 values after 48 h incubation) representative of all flavonoids was 5,6-dihydroxyflavone (A375: 36.40 ± 1.82 µM; C32: 47.50 ± 2.37 µM; SCC25: 53.90 ± 2.71 µM), 7,8-dihydroxyflavone (A375: 33.10 ± 1.65 µM; C32: 56.50 ± 2.83 µM; SCC-25: 57.40 ± 2.87 µM) and zapotin (A375: 31.30 ± 1.57 µM; C32: 26.50 ± 1.33 µM; SCC-25: 21.90 ± 1.09 µM). The analysis of DNA biosynthesis inhibition also shows in all cases that 5,6-dihydroxyflavone, 7,8-dihydroxyflavone and zapotin were the dominant compounds with anticancer activity against the studied cell lines. In addition, a statistical analysis was performed to describe the SAR. Further experiments are underway to find the exact mechanism of the anticancer activity of the studied compounds.