Isolation, chemical modification and cytotoxic evaluation of atranorin, the major metabolite of the foliose lichen Parmotrema melanothrix

The foliose lichen, Parmotrema melanothrix was chemically screened for the first time and isolated the depside atranorin in significant quantity (2%) along with methyl 2,4-dihydroxy-3,6-dimethylbenzoate (2) and methyl 3-formyl-2,4-dihydroxy-6-methylbenzoate (3) . In view of its abundance, interesting structural features and significant biological profile, atranorin was subjected to chemical modification and synthesised five diverse analogues in very good yields (70~93%). The synthesised analogues along with the three isolated compounds were evaluated for their cytotoxic potential against a panel of six human cancer cell lines using MTT assay. Among the tested compounds, 1a showed enhanced activity than the parent compound (1) against almost all the tested cell lines. Significantly, 1a showed highest activity (IC50: 15.19 μM) against DU145 cell line. The results indicate that complete protection of the phenolic hydroxyls in the form of acetates enhances the cytotoxicity, especially against prostate cancer cell line (DU 145).