Synthesis, ADME, and In Silico molecular docking study of Novel N-substituted β-Carboline analogs as a potential inhibitor anticancer agent

β-Carboline alkaloids and its derivatives are a significant class of natural products and pharmaceutically important molecules, which display their anticancer activities via diverse mechanisms. Since last one decade, β-carboline analogs have attained interest as anti-cancer agents and have been extensively isolated, synthesized and tested against cancer cell line. β-carboline derivatives exhibit potent anti-cancer activity via diverse mechanisms such as interfering with enzymes like CDKs (cyclin-dependent kinases), IκB kinases TOPO-I and II, and intercalating DNA. Selected list anticancer β-carboline alkaloid and synthetic derivatives²⁷ are listed.

The present study designed and computationally optimized a series of novel β-carboline derivatives to investigate the interaction between designed ligands and selected proteins. Therefore, to find better intercalating agents, β-carboline was used as a basic skeleton, and a series of novel β-carboline derivatives with various aryl group groups at C-1 sites and an ethyl acetyl, benzyl group at N-9 position were designed. In silico docking, the study was performed to determine the maximum interaction between designed ligands and with protein 1pye CDK₂ inhibitor. The best binding post with a minimum energy of the designed ligand was selected for synthesis

The pyrido[3,4-β] indole β-carboline skeleton structure is broadly present in many naturally occurring alkaloids which display diverse and interesting medicinal activities. A few of the biologically important naturally occurring and synthetic β-carboline analogs are shown below: