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

Abstract

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 N 2-benzylated β-carbolinium bromides 56– 60 represented the most potent compounds with IC 50 values lower than 10 μM. The application of 3D-QSAR to these compounds explored the structural basis for their biological activities. CoMFA ( q 2 = 0.513, r 2 = 0.862) and CoMSIA ( q 2 = 0.503, r 2 = 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.