AN OVERVIEW ON TETRAHYDRO-β-CARBOLINE DERIVATIVES AS PROMISING LEADS IN MODERN DRUG DEVELOPMENT

Dr. S. Karthika*, J. Akhash, A. Saranya, R. Saravanan, T. S. Thilagavathi, A. P. Umasneha, Dr. S. Anbazhagan

Tetrahydro-β-carbolines (THβCs), also known as tryptolines, are structurally diverse heterocyclic alkaloids composed of a tricyclic pyrido [3,4-b] indole nucleus. They are naturally present in various plants such as Peganum harmala, marine organisms, and have emerged as privileged scaffolds in medicinal chemistry due to their interaction with multiple biological targets. The Pictet–Spengler condensation of tryptamine derivatives with aldehydes or ketones represents the principal synthetic route to THβCs, enabling the generation of structurally diverse analogues including cis and trans isomers. Numerous synthetic modifications, including asymmetric catalysis, metal-mediated cyclization’s, and microwave- assisted protocols, have been developed to improve reaction efficiency and stereoselectivity. THβCs exhibit a broad range of biological activities such as anticancer, antimicrobial, antileishmanial, antimalarial, antioxidant, neuroprotective, and antiinflammatory effects. They modulate critical enzymes and receptors, including monoamine oxidase and serotonin pathways, underscoring their potential in treating neurodegenerative and psychiatric disorders. This comprehensive review highlights advances in THβC synthesis, biological evaluation, and therapeutic applications, emphasizing for future research directions for drug development.