Isolation, Characterization, and Breast Cancer Cytotoxic Activity of Gyrophoric Acid from the Lichen Umbilicaria muhlenbergii

Abstract

Lichens produce a large variety of secondary metabolites with diverse bioactivities, chemical structures, and physicochemical properties. For this reason, there is a growing interest in the use of lichen-derived bioactive molecules for drug discovery and development. Here, we report on the isolation, identification, and cytotoxic evaluation of gyrophoric acid (GA) from the lichen Umbilicaria muhlenbergii, a largely unexplored and scantly described lichen species. A simple purification protocol was developed for the fractionation of lichen crude extracts with silica gel column chromatography using solvents with changing polarity. GA was identified in one of the fractions with Fourier transform infrared spectroscopy (FTIR), ion trap mass spectrometry (MS), and nuclear magnetic resonance spectroscopy (1H-NMR and 13C-NMR). The FTIR spectra demonstrated the presence of aromatic and ester functional groups C=C, C-H, and C=O bonds, with the most remarkable signals recorded at 1400 cm−1 for the aromatic region, at 1400 cm−1 for the CH3 groups, and at 1650 cm−1 for the carbonyl groups in GA. The MS spectra showed a molecular ion [M-1]− at (m/z) 467 with a molecular weight of 468.4 and the molecular formula C24H20O10. that correspond to GA. The 1H-NMR and 13C-NMR spectra verified the chemical shifts that are typical for GA. GA reduced the cell viability of breast cancer cells from the MCF-7 cell line by 98%, which is indicative of the strong cytotoxic properties of GA and its significant potential to serve as a potent anticancer drug.

Tridepsides as potential bioactives: a review on their chemistry and the global distribution of their lichenic and non-lichenic natural sources

“…Multiple studies have examined the potential antiproliferative effect of GA (ESM-1, Table S1). In the most recent study, Mohammadi et al (2022) showed the potent cytotoxicity of GA against breast cancer cell lines. The antiproliferative activity of this compound has also been demonstrated against several other cancer cell lines.…”

“…Multiple studies have examined the potential antiproliferative effect of GA (ESM-1, Table S1 ). In the most recent study, Mohammadi et al. (2022) showed the potent cytotoxicity of GA against breast cancer cell lines.…”

Uncovering the Anticancer Potential of Lichen Secondary Metabolites

“…The production of ROS leads to DNA damage and changes in the stress/survival pathways activation [13]. GA (300 -500 µg/mL) reduces the viability of breast cancer MCF-7 cells by 98% [61]. GA showed mild cytotoxic activity in MM98 malignant mesothelioma cells, and A431 vulvar carcinoma cells.…”

Special Issue on “Secondary Metabolites: Extraction, Optimization, Identification and Applications in Food, Nutraceutical, and Pharmaceutical Industries”

“…The research of Mohammadi and his coworkers [5] explored Gyrophoric Acid (GA) from the lichen Umbilicaria muhlenbergii for breast cancer cytotoxicity. A purification process employing silica gel column chromatography was developed for GA isolation.…”