Synthesis and biological activity of polyalthenol and pentacyclindole analogues

• Synthesis of forty polyalthenol and pentacyclindole analogues, starting from ent-halimic acid is described.
• Pentacyclindole is an indole sesquiterpene that presents a new framework, recently published in the literature.
• All the forty analogues have been tested their antiproliferative activity (GI50) against human solid tumour cells.
• It has been found a lead that present GI50 values in the range 1.2–5.7 μM against all cell lines tested.

A series of indole sesquiterpenes analogues of polyalthenol and pentacyclindole have been synthesized starting from ent-halimic acid in order to test their biological activity. These analogues include diverse oxidation levels at the sesquiterpenyl moiety and different functionalization on the indole ring. All synthetic derivatives were tested against a representative panel of Gram positive and Gram negative bacterial strains, and the human solid tumour cell lines A549 (non-small cell lung), HBL-100 (breast), HeLa (cervix), SW1573 (non-small cell lung), T-47D (breast) and WiDr (colon). Overall, the compounds presented activity against the cancer cell lines. The resulting lead, displaying a polyalthenol scaffold, showed GI50 values in the range 1.2–5.7 μM against all cell lines tested.

Several indole sesquiterpenes analogues of polyalthenol and pentacyclindole have been synthesized starting from ent-halimic acid and tested their antitumoural activity.Figure optionsDownload as PowerPoint slide