Alkaloids from Mackinlaya species and synthetic mackinazolinone derivatives: An overview.

Mackinazolinone is the main alkaloid isolated from plants of the genus Mackinlaya, essentially distributed in tropical Asia and Australia. There are five Mackinlaya species all containing bioactive alkaloids with a tetrahydropyridoquinazolinone core such as mackinazoline (1) and mackinazolinone (2). The present review retraces the origin of mackinazolinone and compares the different chemical routes to synthesize the natural product, through different methods including classical batch synthesis, solid-phase supported synthesis, microwaved irradiation and photochemistry. A panel of about 70 mackinazolinone analogues and derivatives is presented to illustrate the diversity of chemical approaches and structures. The pharmacology of mackinazolinone has been little investigated but derivatives with antibacterial or anticancer properties have been identified. The molecular targets for these compounds are essentially unknown, but a few proteins of interest have been evoked occasionally, such as the EGFR kinase. The natural product mackinazolinone has largely inspired chemists to develop novel products and chemical processes. Hopefully, the review will now encourage pharmacologists to further explore the properties of these quinazolinones as potential anti-infectious, anticancer and/or neuroprotective agents.