Alessandra Giardini

Inhibitors of tubulin polymerization: synthesis and biological evaluation of hybrids of vindoline, anhydrovinblastine and vinorelbine with thiocolchicine, podophyllotoxin and baccatin III.

A series of novel hybrid compounds obtained by the attachment of anhydrovinblastine, vinorelbine, and vindoline to thiocolchicine, podophyllotoxin, and baccatin III are described. Two types of diacyl spacers are introduced. The influence of the hybrid compounds on tubulin polymerization is reported. The results highlight the importance of the length of the spacer. Immunofluorescence microscopy and flow cytometry measurements that compound with the best in vitro activity could disrupt microtubule networks in cell and prevent the formation of the proper spindle apparatus, thereby causing cell cycle arrest in the G2/M phase. The newly synthesized compounds were tested in the human lung cancer cell line A549.

Ibogaine analogues. Synthesis and preliminary pharmacological evaluation of 7-heteroaryl-2-azabicyclo[2.2.2]oct-7-enes.

Synthesis of 7-heteroaryl-2-azabicyclo[2.2.2]oct-7-enes by cycloaddition and subsequent cross-coupling reaction is described. Binding affinity of these novel compounds towards the characteristic receptorial targets of ibogaine is illustrated.

A convenient synthesis of Δ7,8-morphinan-6-one and its direct oxidation to 14-hydroxy-Δ7,8-morphinan-6-one

Abstract Synthesis of Δ 7,8 -morphinan-6-one by Grewe cyclization and bromoketalization reaction as crucial steps is described. Introduction of a hydroxyl group at 14-position is demonstrated by direct oxidation with MnO 2 in the presence of silica gel.

Cyclodimerization of indol-2-ylacetylenes. An example of intermolecular enyne–alkyne cycloaddition

Cyclodimerization of methyl 3-(indol-2-yl)propiolate 1 and 2-(indol-2-yl)-1-(phenylsulfonyl)acetylene 2 proceeds through an enyne–alkyne cycloaddition to give 4-(indol-2-yl)carbazoles.