Synthesis and Biological Screening of New Cyano-Substituted Pyrrole Fused (Iso)Quinoline Derivatives.

Maria Cristina Al-Matarneh,Roxana-Maria Amărandi,Ramona Danac,Ionel I Mangalagiu

doi:10.3390/molecules26072066

Abstract

Several new cyano-substituted derivatives with pyrrolo[1,2-a]quinoline and pyrrolo[2,1-a]isoquinoline scaffolds were synthesized by the [3 + 2] cycloaddition of (iso)quinolinium ylides to fumaronitrile. The cycloimmonium ylides reacted in situ as 1,3-dipoles with fumaronitrile to selectively form distinct final compounds, depending on the structure of the (iso)quinolinium salt. Eleven compounds were evaluated for their anticancer activity against a panel of 60 human cancer cell lines. The most potent compound 9a showed a broad spectrum of antiproliferative activity against cancer cell lines representing leukemia, melanoma and cancer of lung, colon, central nervous system, ovary, kidney, breast and prostate cancer. In vitro assays and molecular docking revealed tubulin interaction properties of compound 9a.

Highlights

Fused polyazaheterocyclic derivatives are essential structural motifs, being commonly present in natural products and bioactive agents
The pyrrolo[1,2-a]quinoline moiety is present in the natural alkaloid gephyrotoxin, a muscarinic antagonist [12,13], while other pyrrolo[1,2a]quinoline derivatives are known as activators of caspases and inducers of apoptosis by inhibiting tubulin polymerization and effective anticancer agents (Figure 1) [14,15]
[17,18,19,20,21,22], we present the design and Taking into account the abovementioned details, as well as our ongoing interest in synthesis of novel pyrrolo[1,2-a]quinoline and pyrrolo[2,1-a]isoquinoline derivatives which developing new bioactive fused heterocycles [17,18,19,20,21,22], we present the design and show pyrrolo[1,2-a]quinoline great promise as anticancer

Summary

Introduction

Fused polyazaheterocyclic derivatives are essential structural motifs, being commonly present in natural products and bioactive agents. Due to their wide range of biological activities, they represent one of the most important classes of organic compounds, with extensive applications in medicinal chemistry [1]. The pyrrolo[1,2-a]quinoline moiety is present in the natural alkaloid gephyrotoxin, a muscarinic antagonist [12,13], while other pyrrolo[1,2a]quinoline derivatives are known as activators of caspases and inducers of apoptosis by inhibiting tubulin polymerization and effective anticancer agents (Figure 1) [14,15]

Methods

Results

Conclusion