MERIDIANINS: A COMPREHENSIVE REVIEW OF THE CHEMISTRY, SYNTHESIS, AND MULTIFACETED PHARMACOLOGY OF MARINE-DERIVED INDOLE ALKALOIDS

Meridianins are brominated indole alkaloids with a variety of fascinating biological activities that were first discovered in the Antarctic tunicate Aplidium meridianum. This review compiles the structure-activity relationships (SAR), chemistry, and synthesis of this family of natural products and their analogues. Their core 3-(2-aminopyrimidinyl)indole scaffold is accessed through key synthetic methods such as indole protection, C-3 functionalisation, and cyclocondensation. Structural differences, particularly in bromination and hydroxylation patterns, have a major impact on their potent bioactivities, including kinase inhibition, neuroprotection, anti-inflammatory, and anti-cancer effects. This work combines chemical and pharmacological data to highlight the Meridianin framework as a versatile and beneficial scaffold. It provides a basic framework for the rational development of novel therapies targeted at complex diseases, especially neurodegenerative disorders.