Syntheses of Dehydroaltenusin, a Selective Inhibitor of Mammalian DNA Polymerase α

Dehydroaltenusin has been isolated from Alternaria tenuis and other fungal species. It exhibits various biological activities such as growth inhibition of wood-damaging fungi, inhibition of calmodulin-dependent myosin light chain kinase, anti-HIV activity, and inhibition of mammalian DNA polymerase α (pol α). These significant biological activities, as well as the unique structural properties of dehydroaltenusin, have stimulated considerable interest in its synthesis. In this review, we summarize the synthesis and structural analysis of dehydroaltenusin and its derivatives. We also focus on the structure-activity relationships of dehydroaltenusin as a mammalian pol α inhibitor. Dehydroaltenusin specifically inhibits mammalian pol α, an enzyme that plays an important role in DNA replication and cell division. The human genome encodes 14 pols that control cellular DNA synthesis, and synthetic dehydroaltenusin derivatives, which are specific inhibitors of mammalian pol α, are useful tools and molecular probes for distinguishing pols and for clarifying their biological and in vivo functions. Moreover, these compounds might be potentially useful as anti-cancer chemotherapeutic drugs for in vivo studies.