Synthesis of Artesunic Acid–Coumarin Hybrids as Potential Antimelanoma Agents

Abstract

Current therapy against melanoma relies on surgical treatment or, in alternative, on conventional drug therapy. Often these therapeutic agents are ineffective due to the development of resistance phenomena. For this purpose, chemical hybridization emerged as an effective strategy to overcome the development of drug resistance. In this study, a series of molecular hybrids were synthesized combining the sesquiterpene artesunic acid with a panel of phytochemical coumarins. Cytotoxicity, antimelanoma effect, and cancer selectivity of the novel compounds were evaluated by MTT assay on primary and metastatic cells and on healthy fibroblasts as a reference. The two most active compounds showed lower cytotoxicity and higher activity against metastatic melanoma than paclitaxel and artesunic acid. Further tests, including cellular proliferation, apoptosis, confocal microscopy, and MTT analyses in the presence of an iron chelating agent, were conducted with the aim of tentatively addressing the mode of action and the pharmacokinetic profile of selected compounds.

Autofluorescent antimalarials by hybridization of artemisinin and coumarin: in vitro/in vivo studies and live-cell imaging

“…We selected bioactive coumarins as prominent and suitable pharmacophores. While few examples of anticancer artemisinin-coumarin hybrids are known, 30–32 no examples of antimalarial artemisinin-coumarin hybrid compounds and their in vitro / in vivo analyses and mode of action studies have been reported to date. Coumarin derivatives e.g.…”

Regulation of Cell Cycle Progression through RB Phosphorylation by Nilotinib and AT-9283 in Human Melanoma A375P Cells

“…Then, they were incubated for 24 h. The Cell Counting Kit-8 solution (10 L) was added to each well, and the mixture was incubated for an additional 3 h at C. The absorbance of each well at 450 nm was measured using a VICTOR Nivo Multimodr Plate Reader. The 50% inhibitory concentrations ( ) of imatinib, nilotinib, AT-9283, and ZM-306416 were calculated using GraphPad Prism software (Version 9.0) [ 47 ].…”