Anti-infective Potential of Manzamine Alkaloids – A Review

Background: From time immemorial, natural products have been used for the treatment of various diseases. Various natural products, their semisynthetic derivatives, and synthetic analogs have been explored for their anti-infective properties. One such group of natural compounds that have been widely explored is manzamine alkaloids. Manzamine alkaloids are complex natural compounds consisting of a β-carboline nucleus attached to a pentacyclic ring system that was first isolated from a marine sponge during the 1980s. Objective: The review aims to provide a critical overview of the anti-infective potential of manzamine alkaloids. Method: A comprehensive and exhaustive review of the literature on manzamine alkaloids consisting of their isolation, anti-infective properties, and mechanism of action is presented. Results: Various manzamine alkaloids have been isolated and found to exhibit potent anti-infective activities like antibacterial, antimalarial, antiviral, antifungal, antileishmanial, among others. These manzamine alkaloids exhibit their anti-infective activity by inhibiting targets like GSK-3β and MtSK. Conclusion: This present review with structure-activity relationship study of manzamine alkaloids for their anti-infective activity will be useful for further development of semisynthetic manzamine analogs as potent anti-infective agents with better therapeutic potential and reduced toxicity.

Synthesis of the tricyclic core of manzamine A

An approach to the ABC tricyclic ring system of the manzamine alkaloids has been achieved. A key step is the intramolecular dipolar cycloaddition of an azomethine ylide.