Integration of LC/MS, NMR and Molecular Docking for Profiling of Bioactive Diterpenes from Euphorbia mauritanica L. with in Vitro Anti-SARS-CoV-2 Activity.

In spite of tremendous efforts exerted in the management of COVID-19, the absence of specific treatments and the prevalence of delayed and long-term complications termed post-COVID syndrome still urged all concerned researchers to develop a potent inhibitor of SARS-Cov-2. The hydromethanolic extracts of different parts of E. mauritanica were in vitro screened for anti-SARS-Cov-2 activity. Then, using an integrated strategy of LC/MS/MS, molecular networking and NMR, the chemical profile of the active extract was determined. To determine the optimum target for these compounds, docking experiments of the active extract's identified compounds were conducted at several viral targets. The leaves extract showed the best inhibitory effect with IC50 8.231±0.04 µg/ml. The jatrophane diterpenes were provisionally annotated as the primary metabolites of the bioactive leaves extract based on multiplex of LC/MS/MS, molecular network, and NMR. In silico studies revealed the potentiality of the compounds in the most active extract to 3CLpro, where compound 20 showed the best binding affinity. Further attention should be paid to the isolation of various jatrophane diterpenes from Euphorbia and evaluating their effects on SARS-Cov-2 and its molecular targets.

Prevalence of Diterpenes in Essential Oil of Euphorbia mauritanica L.: Detailed Chemical Profile, Antioxidant, Cytotoxic and Phytotoxic Activities.

Plants belonging to Euphorbia L. genus are considered very interesting from a medicinal point of view due to their diverse metabolites and bioactivities. The essential oil (EO) of Euphorbia mauritanica L. is not studied up to date. Therefore, the present study aimed to explore the chemical profile of this EO and evaluate its antioxidant, cytotoxic, and allelopathic potentialities. The EO was extracted from the whole plant via hydrodistillation and then, analyzed by gas chromatography/mass spectrometry (GC/MS). The correlation of E. mauritanica with the other Euphorbia plants was established using chemometric analysis. The antioxidant activity was determined based on scavenging of the free radical, 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). The anti-proliferation of the EO on the Hep G2 and MCF-7 cells was evaluated. Finally the allelopathic activity of the EO was assessed against the two noxious weeds, Dactyloctenium aegyptium and Urospermum picroides. Forty-one compounds were identified using GC/MS analysis, with an abundance of terpenoids (91.54 %) that were categorized into mono- (30.75 %), sesqui- (15.23 %), and diterpenes (45.56 %). Interestingly, the results revealed the preponderance of diterpenoid constituents although they are rarely found in the EOs of the plant kingdom. The major compounds were (3E)-cembrene A (18.66 %), verticiol (17.05 %), limonene (7.91 %), eucalyptol (7.26 %), α-pinene (5.61 %), neo-cembrene A (3.52 %), kaur-16-ene (3.24 %), and cembrene (3.09 %). The EO showed moderate antioxidant activity where it attained IC50 values of 83.34 and 64.21 µg mL-1 for DPPH and ABTS compared to 23.01 and 19.23 µg mL-1 for ascorbic acid as standard, respectively. The EO exhibited very weak cytotoxic effect on MCF-7 and Hep G2 cells. The EO showed significant allelopathic activities against the weeds D. aegyptium and U. picroides in a concentration-dependent manner. EO was found more effective against U. picroides than D. aegyptium with IC50 values of 0.79, 0.45, and 0.67 mg mL-1 and 1.17, 0.55, and 1.08 mg mL-1 for germination, root, and shoot growth, respectively. Due to the high content of diterpenes in E. mauritanica, further study is recommended for more characterization of pure forms of the identified diterpenes as well as evaluating their bioactivity either solely or synergistically.

Characterization of undescribed melanoma inhibitors from Euphorbia mauritanica L. cultivated in Egypt targeting BRAFV600E and MEK 1 kinases via in-silico study and ADME prediction.

Three undescribed diterpenes including two ent-abietanes, euphomauritanol A, and euphomauritanol B, and one jatrophane, euphomauritanophane A, in addition to eight previously described metabolites were isolated from the MeOH-CH2Cl2 (1:1) extract of the Euphorbia mauritanica. The chemical structures of isolates were established based on the spectroscopic means including FT-IR, HRMS, 1D and 2D NMR. The absolute stereochemistry of the undescribed diterpenes was deduced by experimental and calculated TDDFT-electronic circular dichroism (ECD). The anti-proliferative effects of the isolated diterpenes were evaluated against B16-BL6, Hep G2, and Caco-2. The euphomauritanol A, euphomauritanol B, and euphomauritanophane A significantly inhibited the growth of murine melanoma B16-BL6 cell lines with IC50 10.28, 20.22, and 38.81 µM, respectively with no responses against the other cells. These activities were rationalized by molecular docking of the active compounds in BRAFV600E and MEK1 active sites. Moreover, the in-silico pharmacokinetics predictions by Swiss ADME revealed that the active compounds possessed favorable oral bioavailability and drug-likeness properties.