A library of hybrid and dimer compounds based on the natural scaffold of artemisinin was synthesized. These derivatives were obtained by coupling of artemisinin derivatives, artesunate, and dihydroartemisinin with a panel of phytochemical compounds. The novel artemisinin-based hybrids and dimers were evaluated for their anticancer activity on a cervical cancer cell line (HeLa) and on three complementary metastatic melanoma cancer cell lines (SK-MEL3, SK-MEL24, and RPMI-7951). Two hybrid compounds obtained by coupling of artesunate with eugenol and tyrosol, and one of the dimer compounds containing curcumin, emerged as the most active and cancer-selective derivatives.

Stilbene and chalcone derivatives with biological activity against influenza A virus have been synthesized by self-, cross-, and ring-closing metathesis procedures. The reactions were performed under environmentally friendly conditions using the second generation Hoveyda-Grubbs catalyst Aquamet SiPr after immobilization on Santa Barbara Amorphous mesoporous silicate SBA-15. Irrespective from the experimental conditions, the heterogeneous catalyst showed activity and selectivity comparable than the homogeneous counterpart for at least six successive runs without appreciable leaching of the active species. An appreciable antiviral activity against influenza A virus for some of the novel derivatives were observed, mainly involving the early stage of the virus-replication life-cycle.

Artesunic acid and artemisinin are natural substances with promiscuous anticancer activity against different types of cancer cell lines. The mechanism of action of these compounds is associated with the formation of reactive radical species by cleavage of the sesquiterpene pharmacophore endoperoxide bridge. Here we suggested topoisomerase 1 as a possible molecular target for the improvement of the anticancer activity of these compounds. In this context, we report that novel hybrid and dimer derivatives of artesunic acid and artemisinin, bearing camptothecin and SN38 as side-chain biological effectors, can inhibit growth of yeast cells overexpressing human topoisomerase 1 and its enzymatic activity in vitro. These derivatives showed also anticancer activity in melanoma cell lines higher than camptothecin and paclitaxel. In silico molecular docking calculations highlighted a common binding mode for the novel derivatives, with the sesquiterpene lactone scaffold being located near the traditional recognition site for camptothecin, while the bioactive side-chain effector laid in the camptothecin cleft.

A blue‐LED‐driven two‐liquid‐phase system has been set up for the in situ activation of horseradish peroxidase avoiding the use of hydrogen peroxide and drawbacks related to enzyme denaturation and undesired radical side‐reactions. The photobiocatalytic system was applied for the oxidative coupling of natural and synthetic coumarins to bicoumarins, allowing to obtain homodimers in only one step, avoiding the use of tedious protecting groups. Two natural C‐2 symmetric bicoumarins derived from the coupling of scopoletin were synthesized for the first time. UV‐visible spectrophotometry analysis confirmed the radical‐free and blue‐LED‐driven in situ oxidation of the green solvent 2‐methyltetrahydrofuran to the corresponding hydroperoxide, which in turn oxidizes the ferric heme of horseradish peroxidase to ferryl intermediate, triggering the oxidative coupling reaction.

Background: Multicomponent reactions are one-pot processes for the synthesis of highly functionalized hetero-cyclic and hetero-acyclic compounds, often endowed with biological activity. Objective: Multicomponent reactions are considered green processes with high atom economy. In addition, they present advantages compared to the classic synthetic methods such as high efficiency and low wastes production. Method: In these reactions two or more reagents are combined together in the same flask to yield a product containing almost all the atoms of the starting materials. Results: The scope of this review is to present an overview of the application of multicomponent reactions in the synthesis of compounds endowed with antiviral activity. The syntheses are classified depending on the viral target. Conclusion: Multicomponent reactions can be applied to all the stages of the drug discovery and development process making them very useful in the search for new agents active against emerging (viral) pathogens.

Belladine N-oxides active against influenza A virus have been synthetized by a novel laccase-catalyzed 1,4-dioxane-mediated oxidation of aromatic and side-chain modified belladine derivatives. Electron paramagnetic resonance (EPR) analysis confirmed the role of 1,4-dioxane as a co-oxidant. The reaction was chemo-selective, showing a high functional-group compatibility. The novel belladine N-oxides were active against influenza A virus, involving the early stage of the virus replication life cycle.

Laccase-mediated intramolecular oxidative radical coupling of N-formyl-2-bromo-O-methylnorbelladine afforded a novel and isolable spirocyclohexadienonic intermediate of galantamine.

A photochemoenzymatic halodecarboxylation of ferulic acid was achieved using vanadate-dependent chloroperoxidase as (bio)catalyst and oxygen and organic solvent as sole stoichio-metric reagents in a biphasic system. Performance and selectivity were improved through a phase transfer catalyst, reaching a turnover number of 660.000 for the enzyme.