In silico and in vitro degradation studies of isolated phloroglucinols eugenial C and eugenial D from Eugenia umbelliflora fruits

Introduction Eugenia umbelliflora fruits are an important source of phloroglucinols, as eugenial C and eugenial D, related to antimicrobial activity against Staphylococcus aureus. However, for the establishment of new antimicrobial substances, it is essential to know their stability profile, in view...

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Published in:Phytochemical analysis 2020-03, Vol.31 (2), p.221-228
Main Authors: Farias, Ingrid V., Amorin, Clarissa Krieger, Santos, Milena Guimarães, Santos Machado, Carmem Lúcia, Paula, Favero Reisdorfer, Sandjo, Louis P., Malheiros, Angela, Meyre‐Silva, Christiane, Bresolin, Tania Mari Bellé
Format: Article
Language:English
Subjects:
Antiinfectives and antibacterials
Antimicrobial activity
Antimicrobial agents
Chromatography, High Pressure Liquid
Degradation
degradation products
Drug Stability
Environmental conditions
Eugenia
Fruit
Fruits
High performance liquid chromatography
Hydrochloric acid
Hydrogen peroxide
Hydrolysis
In vitro methods and tests
Liquid chromatography
meroterpenoids
Oral administration
Oxidation
Oxidation-Reduction
Phloroglucinol
Photosensitivity
pre‐formulation study
Relative humidity
Sodium hydroxide
stress test
Ultraviolet detectors
Ultraviolet radiation
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Summary:Introduction Eugenia umbelliflora fruits are an important source of phloroglucinols, as eugenial C and eugenial D, related to antimicrobial activity against Staphylococcus aureus. However, for the establishment of new antimicrobial substances, it is essential to know their stability profile, in view of driving the administration route and the release system development. Methodology The in silico approaches, based on the Fukui indices and bond dissociation analysis, were performed. Eugenial C and eugenial D, isolated from the green fruits of E. umbelliflora, with purity > 90%, were submitted to stress degradation including: acid (0.5 mM hydrochloric acid) and alkaline (0.5 mM sodium hydroxide) hydrolysis, and oxidation (0.25% hydrogen peroxide), in different periods, monitoring by high‐performance liquid chromatography with ultraviolet detector (HPLC‐UV). Eugenial C was also submitted to UV‐visible radiation (2,400 lux/h) and dry/humid heating (40°C, 75% relative humidity). Results In silico studies indicated that both molecules have regions of high susceptibility to nucleophilic and electrophilic attack as well as sites likely to suffer auto‐oxidation. Under in vitro tests, both phloroglucinols proved to be very unstable under hydrolysis (eugenial C and D were degraded 23.8% and 89.0% in acid and 78.4% and 97.8% in alkaline conditions, respectively) and oxidation (eugenial C and D degraded 31.9% and 28.6%, respectively), both during 5 min. Eugenial C degraded 12.6% and 63.8% under dry and humid heat, respectively, without photosensitivity. Conclusion The in vitro stress tests monitored by HPLC‐UV were in agreement with in silico degradation prediction. Phloroglucinols could be unstable if administered by oral route and also under environmental conditions demanding a protective release system. Two phloroglucinols were isolated from Eugenia umbelliflora, eugenial C and engenial D, which demonstrated antimicrobial activity. Both phloroglucinols, showed be very unstable under hydrolysis and oxidation conditions, being eugenial D more susceptible than eugenial C. The eugenial C also showed to be thermosensivite, but photostable. In silico studies indicated the regions of greater susceptibility to nucleophilic, electrophilic attack and the sites to suffer auto‐oxidation. The results point out the need to develop a protective release system to these potential phytodrugs.
ISSN:0958-0344
1099-1565
DOI:10.1002/pca.2885