Manzamine A

Manzamine A is a β-carboline alkaloid with diverse activities that has been found in marine sponges, including X. ashmorica. It is an inhibitor of glycogen synthase kinase 3β (GSK3β) and cyclin-dependent kinase 5 (CDK5; IC50s = 10.2 and 1.5 μM, respectively). It inhibits the growth of L5178y mouse lymphoma cells with an ED50 value of 1.8 μg/mL. In an agar diffusion assay, manzamine A inhibits the growth of B. subtilis and S. aureus, but not E. coli bacteria. It reduces the reverse transcriptase (RT) activity in supernatant from HIV-1-infected peripheral blood mononuclear cells (PBMCs; EC50 = 4.2 μM). In vivo, manzamine A (100 μmol/kg, i.p.) has antimalarial activity and reduces the amount of P. berghei in infected mice by over 90% relative to the control. Manzamine A (132 ppm) inhibits the growth of S. littoralis larva by 80% when added to the larval diet.