| Summary: | New quinazolinone derivatives of the marine-derived alkaloids fiscalin B (<b>3</b>) and fumiquinazoline G (<b>1</b>), with neuroprotective and antitumor effects, were synthesized. Eleven quinazolinone-containing indole alkaloids were synthesized, proceeding the <i>anti</i> analogs via a one-pot method, and the <i>syn</i> analogs by the Mazurkiewicz-Ganesan approach. The neuroprotection capacity of these compounds on the rotenone-damage human neuroblastoma cell SH-SY5y was evaluated using the MTT assay. Compounds <b>1</b>, <b>3</b>, <b>5</b>, and <b>7</b> showed more than 25% protection. The antitumor activity was investigated using the sulforhodamine B assay and some compounds were tested on the non-malignant MCF-12A cells. Fumiquinazoline G (<b>1</b>) was the most potent compound, with GI<sub>50</sub> values lower than 20 µM. Compounds <b>5</b>, <b>7</b>, and <b>11</b> were more active in all tumor cell lines when compared to their enantiomers. Compounds <b>5</b>, <b>7</b>, <b>10</b>, and <b>11</b> had very little effect in the viability of the non-malignant cells. Differences between enantiomeric pairs were also noted as being essential for these activities the <i>S</i>-configuration at C-4. These results reinforce the previously described activities of the fiscalin B (<b>3</b>) as substance P inhibitor and fumiquinazoline G (<b>1</b>) as antitumor agent showing potential as lead compounds for the development of drugs for treatment of neurodegenerative disorders and cancer, respectively.
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