Exploring the Anticancer Potential of Synthetic β-Carboline Derivatives: A Comprehensive Systematic Review

Cancer remains a formidable global challenge, necessitating continuous exploration of innovative therapeutic avenues. Synthetic β-carboline derivatives have emerged as promising candidates with notable anticancer properties. This systematic review comprehensively investigates the anticancer potential of synthetically developed β-carboline derivatives, including monomers, derivatives, bivalents/dimeric compounds, hybrids (e.g., chalcone, indole, hydroxamate, cinnamate, amino acid esters), metal complexes (ruthenium, copper, nickel, etc.), tetrahydro-β- carbolines, and others reported over the last twenty two years (2004-2026). The review focuses on their chemistry, synthesis strategies, pharmacology, and mechanisms of action.

A comprehensive literature search was conducted using PubMed, Embase, Web of Science, and Scopus databases. A total of 270 studies were included after rigorous screening and evaluation based on predefined inclusion criteria. Data extraction and synthesis emphasized key findings related to β-carboline derivatives' anticancer activities, structure-activity relationships, and mechanistic insights.

Synthetic β-carboline derivatives exhibit diverse anticancer mechanisms, including DNA binding, induction of apoptosis, and suppression of tumorigenic mediators. These compounds demonstrated significant therapeutic potential in both in vitro and in vivo models. Notable findings highlighted their efficacy, chemical modifications, and structural features that contribute to enhanced anticancer activity.

The collective evidence underscores that β-carboline derivatives act through multiple molecular targets and signalling pathways. Their structure-activity relationships and mechanistic data suggest potential for optimization in medicinal chemistry. Moreover, integration of in silico approaches and metal complex formation has further broadened their therapeutic scope.

Synthetic β-carboline derivatives represent a promising class of anticancer agents. Insights from this review may guide future drug discovery efforts and support the development of novel β-carboline-derived therapeutics with improved effectiveness and minimized adverse effects.