Chemistry of trisindolines: natural occurrence, synthesis and bioactivity

Heterocyclic nitrogen compounds are privileged structures with many applications in the pharmaceutical and nutraceutical industries since they possess wide bioactivities. Trisindolines are heterocyclic nitrogen compounds consisting of an isatin core bearing two indole moieties. Trisindolines have been synthesized by reacting isatins with indoles using various routes and the yield greatly depends on the catalyst used, reaction conditions, and the substituents on both the isatin and indole moieties. Amongst the synthetic routes, acid-catalyzed condensation reaction between isatins and indoles are the most useful due to high yield, wide scope and short reaction times. Trisindolines are biologically active compounds and show anticancer, antimicrobial, antitubercular, antifungal, anticonvulsant, spermicidal, and antioxidant activities, among others. Trisindolines have not previously been reviewed. Therefore, this review aims to provide a comprehensive account of trisindolines including their natural occurrence, routes of synthesis, and biological activities. It aims to inspire the discovery of lead trisindoline drug candidates for further development. This in-depth review of trisindolines covers their natural occurrence in addition to several routes of synthesis and catalysts used. The biological activities of trisindolines have been discussed with a special emphasis on the structure-activity relationship.