Synthesis of Artesunic Acid-Coumarin Hybrids as Potential Antimelanoma Agents

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.

Automated summary

Current therapy against melanoma relies on surgical treatment or conventional drug therapy, but these methods are often ineffective due to drug resistance. Chemical hybridization has emerged as an effective strategy to overcome drug resistance. In this study, a series of molecular hybrids were synthesized combining artesunic acid with coumarins. The novel compounds showed lower cytotoxicity and higher activity against metastatic melanoma than standard drugs. Further tests were conducted to explore the mode of action and pharmacokinetic profile of selected compounds.