Identification of Anti-Proliferative Compounds from Genista monspessulana Seeds through Covariate-Based Integration of Chemical Fingerprints and Bioactivity Datasets

Abstract

Genista monspessulana (L.) L.A.S. Johnson (Fabaceae) is a Mediterranean plant introduced to South America and other regions for ornamental purposes. However, it is considered an invasive shrub due to its reproductive vigor in many areas. Unlike other Genista plants, G. monspessulana has few studies disclosing its biologically active components, particularly cytotoxic agents against cancer cells. Thus, as part of our research on anti-proliferative bioactives, a set of ethanolic seed extracts from ten accessions of G. monspessulana, collected in the Bogotá plateau, were evaluated against four cell lines: PC-3 (prostate adenocarcinoma), SiHa (cervical carcinoma), A549 (lung carcinoma), and L929 (normal mouse fibroblasts). Extracts were also analyzed through liquid chromatography coupled with mass spectrometry (LC/MS) to record chemical fingerprints and determine the composition and metabolite variability between accessions. Using multiple covariate statistics, chemical and bioactivity datasets were integrated to recognize patterns and identify bioactive compounds among studied extracts. G. monspessulana seed-derived extracts exhibited dose-dependent antiproliferative activity on PC-3 and SiHa cell lines (>500 µg/mL < IC50 < 26.3 µg/mL). Seven compounds (1–7) were inferred as the compounds most likely responsible for the observed anti-proliferative activity and subsequently isolated and identified by spectroscopic techniques. A tricyclic quinolizidine (1) and a pyranoisoflavone (2) were found to be the most active compounds, exhibiting selectivity against PC-3 cell lines (IC50 < 18.6 µM). These compounds were used as precursors to obtain a quinolizidine-pyranoisoflavone adduct via Betti reaction, improving the activity against PC-3 and comparable to curcumin as the positive control. Results indicated that this composition–activity associative approach is advantageous to finding those bioactive principles efficiently within active extracts. This correlative association can be employed in further studies focused on the targeted isolation of anti-proliferative compounds from Genista plants and accessions.

Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Therapeutics

“…Overall, the many exciting findings newly described [6][7][8][9][10][11][12][13] and reviewed [14][15][16][17] in this Special Issue can confidently lead us to a simple conclusion: natural products have a very bright future in the drug research of the 21st century!…”

“…The contributions to this Special Issue demonstrate the huge potential that NPs continue to possess as hits and leads for developing prospective new drugs. Besides a strong focus on the identification and characterization of many new and very promising biologically active NPs against cancer [6][7][8][9][10], infective/parasitic diseases, including their vectors [9,12,13], and diabetic kidney disease [11], it is worth emphasizing that new approaches and methodologies for NP-related drug research are an important focus of this SI. Thus, new methods to identify new bioactive entities in the complex matrices of extracts using hyphenated analytical techniques in combination with computer-aided data analysis tools (e.g., multivariate statistics, molecular networking) are the focus of several articles [6,7,12] utilizing them successfully to identify new bioactive hits.…”

“…Besides a strong focus on the identification and characterization of many new and very promising biologically active NPs against cancer [6][7][8][9][10], infective/parasitic diseases, including their vectors [9,12,13], and diabetic kidney disease [11], it is worth emphasizing that new approaches and methodologies for NP-related drug research are an important focus of this SI. Thus, new methods to identify new bioactive entities in the complex matrices of extracts using hyphenated analytical techniques in combination with computer-aided data analysis tools (e.g., multivariate statistics, molecular networking) are the focus of several articles [6,7,12] utilizing them successfully to identify new bioactive hits. Such techniques provide a holistic evaluation of the active principle(s) in a candidate organism/extract under study in a short time and with little financial effort, so that they are now becoming increasingly important.…”

“…The bio-guided fractionation of C. lipii led to the isolation of cynaropicrin, a sesquiterpene lactone with a promising cytotoxic activity against the CCRF-CEM leukemia cell line (IC 50 = 1.82 µM). Using a similar approach, Diaz et al employed an integrative study on antiproliferative activity against three human cancer cell lines (i.e., PC-3, SiHa, and A549) and the LC-MS chemical profiles of seed extracts from ten accessions of Genista monspessulana [7]. Seven compounds were recognized as responsible for the perceived activity through multiple covariate statistics (15.8 µM < IC 50 < 34.3 µM).…”

Teline monspessulana Can Harm the Chilean Native Tree Nothofagus obliqua: Effects on Germination and Initial Growth

“…In Chilean conditions, this species forms dense populations that eliminate the native vegetation, affect local fauna, interrupt water flows, alter soil nutrient cycles and increase the risk of propagation and intensity of forest fires [21]. The presence of quinolizidine alkaloids, flavonoids and isoflavones has been reported in aerial organs of T. monspessulana [23][24][25], but to our knowledge there are no previous studies of the allelopathic effect of the compounds released by this species. For both phenols and alkaloids, an allelopathic effect has been reported associated with the inhibition of germination, rooting and growth of other plants, the reduction in biomass, and chlorophyll accumulation [26].…”