Manzamine alkaloids: isolation, cytotoxicity, antimalarial activity and SAR studies

• Decreased susceptibility to ACT increased the need for new antimalarial drugs.
• Manzamine A is one of the most potent lead molecules developed as a novel antimalarial agent.
• In vivo cytotoxicity is the major drawback with manzamines.
• SAR of manzamines will be useful to develop potent antimalarial agents with good SI.

The infectious disease Malaria is caused by different species of the genus Plasmodium. Resistance to quinoline antimalarial drugs and decreased susceptibility to artemisinin-based combination therapy have increased the need for novel antimalarial agents. Historically, natural products have been used for the treatment of infectious diseases. Identification of natural products and their semi-synthetic derivatives with potent antimalarial activity is an important method for developing novel antimalarial agents. Manzamine alkaloids are a unique group of β-carboline alkaloids isolated from various species of marine sponge displaying potent antimalarial activity against drug-sensitive and -resistant strains of Plasmodium. In this review, we demonstrate antimalarial potency, cytotoxicity and antimalarial SAR of manzamine alkaloids.