3- O -Methylquercetin from Achyrocline satureioides —cytotoxic activity against A375-derived human melanoma cell lines and its incorporation into cyclodextrins-hydrogels for topical administration

3 -O -Methylquercetin (3 O MQ), a natural 3- O- methylflavonoid, was isolated from Achyrocline satureioides and purified using the high-performance counter current chromatography (HPCCC) on a semi-preparative scale. High-purity 3 O MQ (98%) was obtained with excellent recovery (81.8% (w/w)) and good yield (190 mg/100 g of plant). Isolated 3 O MQ was evaluated against the A375 human amelanotic melanoma cancer cell line and A375-derived with different degrees of aggressiveness (A375-A7, A375-G10, and A375-PCDNA3). The results showed that 3 O MQ reduced the cell viability of all strains, demonstrating time- and dose-dependent responses. 3 O MQ was used to obtain hydrogels for the topical treatment of melanoma. Thus, 3 O MQ was incorporated into hypromellose hydrogels with/without different cyclodextrins (CDs). The 3 O MQ formulations showed permeation/retention in all skin layers, namely stratum corneum, epidermis, and dermis. A significant amount of 3 O MQ was found in the replication site of the melanoma cells (epidermis and dermis). Altogether, these results demonstrate that 3 O MQ can be isolated from Achyrocline satureioides by HPCCC on a semi-preparative scale and exhibit cytotoxic activity against melanoma cells. Its incorporation into an HPMC hydrogel containing HP-β-CD yielded a formulation with excellent technological and biopharmaceutical characteristics for evaluating the topical management of melanoma. Graphical abstract