Targeted Isolation of Indolopyridoquinazoline Alkaloids from Conchocarpus fontanesianus Based on Molecular Networks

Abstract

A dichloromethane-soluble fraction of the stem bark of Conchocarpus fontanesianus showed antifungal activity against Candida albicans in a bioautography assay. Off-line high-pressure liquid chromatography activity-based profiling of this extract enabled a precise localization of the compounds responsible for the antifungal activity that were isolated and identified as the known compounds flindersine (17) and 8-methoxyflindersine (18). As well as the identification of the bioactive principles, the ultra-high-pressure liquid chromatography-high-resolution mass spectrometry metabolite profiling of the dichloromethane stem bark fraction allowed the detection of more than 1000 components. Some of these could be assigned putatively to secondary metabolites previously isolated from the family Rutaceae. Generation of a molecular network based on MS(2) spectra indicated the presence of indolopyridoquinazoline alkaloids and related scaffolds. Efficient targeted isolation of these compounds was performed by geometric transfer of the analytical high-pressure liquid chromatography profiling conditions to preparative medium-pressure liquid chromatography. This yielded six new indolopyridoquinazoline alkaloids (5, 16, 19-22) that were assigned structurally. The medium-pressure liquid chromatography separations afforded additionally 16 other compounds. This work has demonstrated the usefulness of molecular networks to target the isolation of new natural products and the value of this approach for dereplication. A detailed analysis of the constituents of the stem bark of C. fontanesianus was conducted.

Biologically active quinoline and quinazoline alkaloids part II

“…Its MIC values against bacteria Bacillus subtilis , S. aureus , S. epidermidis , Enterococcus faecalis , P. aeruginosa , and Acinetobacter baumannii and fungi Trichophyton rubrum 57, T. mentagrophytes , T. simii , Epidermophyton floccosum , Magnaporthe grisea , and Candida albicans were 31.25, 62.5, 62.5, 31.25, 250, 125, 62.5, 62.5, 62.5, 62.5, 250, and 250 μg/mL . The analog 8‐methoxyflindersine exhibited similar inhibitory activity against the C. albicans ‐sensitive mutant strain DSY2621, but was inactive against a wild strain of this yeast . Meanwhile, the structurally related veprisine showed moderate activity against S. aureus …”

“…The analog 8-methoxyflindersine exhibited similar inhibitory activity against the C. albicans-sensitive mutant strain DSY2621, but was inactive against a wild strain of this yeast. 116 Meanwhile, the structurally related veprisine showed moderate activity against S. aureus. 117 Furoquinoline alkaloids also exhibit antibacterial and antifungal activities.…”

Total Synthesis of Fontanesine B and Its Isomer: Their Antiproliferative Activity against Human Colorectal Cancer Cells

“…After screening of properties of the synthetic material ( 1 H-and 13 C-NMR data, mass spectrum) closely matched those reported for the natural product, thus confirming its assigned structure. [1] Antiproliferative Activity…”

“…Fontanesines A -C (1 -3), having both pyrano [3,2-e] indole and quinazoline skeleton, were isolated from the stem bark and leaf fractions of Conchocarpus fontanesianus, which was collected in Brazil by Queiroz and co-workers ( Figure 1). [1] To date, these alkaloids have not been fully evaluated biologically, due to limited availability. Fontanesines belong to a rare pyrano [3,2-e]indoloquinazoline alkaloid.…”

Current and Future Perspectives on the Structural Identification of Small Molecules in Biological Systems

“…The validation of single annotation even suing just an in silico match with a given metabolite is improved by the fact that many closely related compounds match similar structures. Application of such methods for the putative and tentative annotation of unknowns have been validated for example in natural product research by targeted MS isolation of new alkaloids after prediction based on MN analysis [117]. …”