Design, synthesis and 3D-QSAR of β-carboline derivatives as potent antitumor agents

In a continuing effort to develop novel β-carbolines endowed with better pharmacological profiles, a series of β-carboline derivatives were designed and synthesized based on the previously developed SARs. Cytotoxicities in vitro of these compounds against a panel of human tumor cell lines were also investigated. The results demonstrated that the N2-benzylated β-carbolinium bromides 56–60 represented the most potent compounds with IC50 values lower than 10 μM. The application of 3D-QSAR to these compounds explored the structural basis for their biological activities. CoMFA (q2 = 0.513, r2 = 0.862) and CoMSIA (q2 = 0.503, r2 = 0.831) models were developed for a set of 47 β-carbolines. The results indicated that the antitumor pharmacophore of these molecules were marked at position-1, -2, -3, -7 and -9 of β-carboline ring.

Graphical abstractThe constructive CoMFA and CoMSIA models with highly predictive capacity provided important structural requirement for further design and synthesis of new β-carboline derivatives as potent antitumor agents.Figure optionsDownload full-size imageDownload as PowerPoint slide