Cytotoxic metabolites from Sinularia levi supported by network pharmacology.

The in-vitro anti-proliferative evaluation of Sinularia levi total extract against three cell lines revealed its potent effect against Caco-2 cell line with IC50 3.3 µg/mL, followed by MCF-7 and HepG-2 with IC50 6.4 µg/mL and 8.5 µg/mL, respectively, in comparison to doxorubicin. Metabolic profiling of S. levi total extract using liquid chromatography coupled with high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS) revealed the presence of phytoconstituents clusters consisting mainly of steroids and terpenoids (1-20), together with five metabolites 21-25, which were additionally isolated and identified through the phytochemical investigation of S. levi total extract through various chromatographic and spectroscopic techniques. The isolated metabolites included one sesquiterpene, two steroids and two diterpenes, among which compounds prostantherol (21) and 12-hydroperoxylsarcoph-10-ene (25) were reported for the first time in Sinularia genus. The cytotoxic potential evaluation of the isolated compounds revealed variable cytotoxic effects against the three tested cell lines. Compound 25 was the most potent with IC50 value of 2.13 ± 0.09, 3.54 ± 0.07 and 5.67 ± 0.08 µg/mL against HepG-2, MCF-7 and Caco-2, respectively, followed by gorgosterol (23) and sarcophine (24). Additionally, network analysis showed that cyclin-dependent kinase 1 (CDK1) was encountered in the mechanism of action of the three cancer types. Molecular docking analysis revealed that CDK1 inhibition could possibly be the reason for the cytotoxic potential.

Niosomes as promising approach for enhancing the cytotoxicity of Hemimycale sp. total crude extract supported with in-silico studies.

The crude extract of Hemimycale sp. marine sponge was evaluated as a cytotoxic drug against different cell lines; whereas it exhibited promising selective activity toward the breast cancer cell line only with IC50 value 199.6 ± 0.00512 µg/ml. Moreover, its cytotoxic activity against the breast cancer cell line was reevaluated upon forming total extract-loaded niosomes. This revealed an IC50 value of 44.35 ± 0.011128 µg/ml, indicating the potential contribution of niosomes in boosting cell penetration and activity as a result. Owing to highlight the bioactive constituents responsible for the cytotoxic activity, metabolomics profiling of Hemimycale sp. was performed using liquid chromatography coupled with high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS) revealing tentative identification of phytoconstituents clusters like as, diterpenes, sesterterpenes and sterols. Additionally, the cytotoxic activity of the crude extract was explained on the molecular level, whereas the dereplicated compounds were evaluated in silico against the Epidermal Growth Factor Receptor tyrosine kinase (EGFR). The sesterterpenoid derivatives phorbaketal A acetate (12) and secoepoxy ansellone A (13) together with mycalol-522 (17) showed the best binding energy.

Isolation and structural characterization of phytoconstituents from leaves of Bignonia binata.

Phytochemical investigation of Bignonia binata leaves led to the isolation of three new compounds: including a glycoside of simple alcohol, namely binatoside (2), 3,4-dihydroxy-N-methyl piperidin-2-one (7), and a phenyl ethanoid glycoside, namely bignanoside C (8), alongside with five known compounds; including a glycoside of simple alcohol; (2S) propane-1,2-diol 1-O-(6-O-caffeoy1)-ß-D-glucopyranoside (1), phenyl ethanoids; leucosceptoside A (3) and plantainoside C (4), and iridoids; ipolamiide (5) and strictoloside (6). The structure of the isolated compounds was elucidated by various spectroscopic methods, including 1 D and 2 D NMR experiments, HR-ESI-MS as well as by comparison with the literature.

Anti-leishmanial and cytotoxic compounds isolated from marine sponge Hemimycale sp.

The methanolic extract of the marine sponge Hemimycale sp. yielded two new compounds; 1-(2'-methyl heptadecyl) phenol (1) and a new pyrazole derivative; 4-(hydroxymethyl)-1H-pyrazol-3-ol (2), together with previously isolated (2'R)-2'-hydroxy-N-((2S,3S,4R)-1,3,4-trihydroxy-16-methylpentadecan-2-yl)docosanamide (3), cholesterol (4), 5, 8-epi-dioxycholest-6-en-3-ol (5) and 3-acetylsesterstatin 3 (6), which were firstly reported from family Hymedesmiidae. Their structure elucidation was based on extensive nuclear magnetic resonance spectroscopy and high resolution-electrospray ionization-mass spectrometry. The isolated compounds were evaluated for their anti-leishmanial and cytotoxic activities. Compound 5 showed remarkable anti-leishmanial activity with IC50 value of 15.8 ± 0.92 µg/mL comparable with the standard miltefosine (IC50 = 3.2 ± 0.07 µg/mL), while compound 3 exhibited noteworthy cytotoxicity against A594 cell line with IC50 value of 29.6 ± 1.68 µg/mL compared to etoposide (IC50 = 10.9 ± 1.30 µg/mL).

Metabolomic profiling and biological evaluations of Spongia irregularis-associated actinomycetes supported by multivariate statistical analysis.

AIM: Metabolomic analysis using LC-HRESIMS of 12 extracts of Spongia irregularis-associated actinomycetes for dereplication purposes in addition to evaluation of cytotoxic and antiviral activities of the extracts. METHODS AND RESULTS: In this study, three actinomycetes belonging to the genera Micromonospora, Streptomyces, and Rhodococcus were recovered from the marine sponge Spongia irregularis. Applying the OSMAC approach, each strain was fermented on four different media, resulting in 12 extracts. All extracts were subjected to metabolomic analysis using LC-HRESIMS for dereplication purposes. Multivariate data statistical analysis was carried out for the differentiation between extracts. Additionally, the cytotoxic and anti-hepatitis C virus (anti-HCV) potentials of extracts were evaluated. Most of extracts showed strong to moderate cytotoxicity effects against HepG-2, CACO-2, and MCF-7 cell lines with a general IC50 range of 2.8-8.9 µg/ml. Moreover, the extracts of Micromonospora sp. UR44 using ISP2 and OLIGO media and Streptomyces sp. UR32 using ISP2 medium exhibited anti-HCV activity with IC50 of 4.5 ± 0.22, 3.8 ± 0.18, and 5.7 ± 0.15 µM, respectively. CONCLUSION: Metabolomic analysis of 12 extracts of S. irregularis-associated actinomycetes led to the identification of a large number of secondary metabolites. Morever, investigation of cytotoxic and antiviral activities of the extracts revealed that only three extracts exhibited antiviral activity and seven extracts exhibited cytotoxic activity.

Ultrastructural, Energy-Dispersive X-ray Spectroscopy, Chemical Study and LC-DAD-QToF Chemical Characterization of Cetraria islandica (L.) Ach.

The lichen Cetraria islandica (L.) Ach. has been used in traditional and modern medicines for its many biological properties such as immunological, immunomodulating, antioxidant, antimicrobial, and anti-inflammatory activities. This species is gaining popularity in the market, with interest from many industries for selling as medicines, dietary supplements, and daily herbal drinks. This study profiled the morpho-anatomical features by light, fluorescence, and scanning electron microscopy; conducted an elemental analysis using energy-dispersive X-ray spectroscopy; and phytochemical analysis was performed using high-resolution mass spectrometry combined with a liquid chromatography system (LC-DAD-QToF) of C. islandica. In total, 37 compounds were identified and characterized based on comparisons with the literature data, retention times, and their mass fragmentation mechanism/s. The identified compounds were classified under five different classes, i.e., depsidones, depsides, dibenzofurans, aliphatic acids, and others that contain simple organic acids in majority. Two major compounds (fumaroprotocetraric acid and cetraric acid) were identified in the aqueous ethanolic and ethanolic extracts of C. islandica lichen. This detailed morpho-anatomical, EDS spectroscopy, and the developed LC-DAD-QToF approach for C. islandica will be important for correct species identification and can serve as a useful tool for taxonomical validation and chemical characterization. Additionally, chemical study of the extract of C. islandica led to isolation and structural elucidation of nine compounds, namely cetraric acid (1), 9'-(O-methyl)protocetraric acid (2), usnic acid (3), ergosterol peroxide (4), oleic acid (5), palmitic acid (6), stearic acid (7), sucrose (8), and arabinitol (9).

Isolation and LC-QToF Characterization of Secondary Metabolites from an Endemic Plant Artemisia heptapotamica Poljak.

Phytochemical investigation of the aerial parts of Artemisia heptapotamica Poljak led to the isolation of ten known compounds, including four alkyl p-coumarates: octadecyl trans-p-coumarate (1), icosy trans-p-coumarate (2), docosyl trans-p-coumarate (3), and tetracosyl trans-p-coumarate (4), one sesquiterpene lactone: santonin (5), four flavonoids; axillarin (6), quercetin 3-O-methyl ether (7), luteolin (8), and quercetin (9), and one phenolic acid derivative: p-coumaric acid (10). The structures of the isolated compounds were identified by various spectroscopic analyses. Additionally, the antimicrobial activity of the total extract and different fractions was screened, and they exhibited no inhibition of the growth of Candida albicans, C. neoformans, Aspergillus fumigatus, methicillin-resistant Staphylococcus aureus (MRS), E. coli, Pseudomonas aeruginosa, Klebsiella pneumonia, and Vancomycin-resistant Enterococci (VRE) at the tested concentrations ranging from 8 to 200 µg/mL. The identification and tentative characterization of the secondary metabolites were conducted using LC-QToF analysis. This method helps in the putative characterization of sesquiterpene lactones, flavonoids, coumarate derivatives, and aliphatic compounds. The developed method identified 43 compounds, of which the majority were sesquiterpene lactones, such as eudesmanolides, germacranolides, and guaianolide derivatives, followed by flavonoids. The proposed LC-QToF method helps develop dereplication strategies and understand the major class of chemicals before proceeding with the isolation of compounds.

Bioassay-Guided Fractionation with Antimalarial and Antimicrobial Activities of Paeonia officinalis.

Bioassay-guided fractionation technique of roots of Paeonia officinalis led to isolation and structure elucidation of seven known compounds, including four monoterpene glycosides: lactiflorin (1), paeoniflorin (4), galloyl paeoniflorin (5), and (Z)-(1S,5R)-ß-pinen-10-yl ß-vicianoside (7); two phenolics: benzoic acid (2) and methyl gallate (3); and one sterol glycoside: ß-sitosterol 3-O-ß-D-glucopyranoside (6). The different fractions and the isolated compounds were evaluated for their antimicrobial and antimalarial activities. Fraction II and III showed antifungal activity against Candida neoformans with IC50 values of 28.11 and 74.37 µg/mL, respectively, compared with the standard fluconazole (IC50 = 4.68 µg/mL), and antibacterial potential against Pseudomonas aeruginosa (IC50 = 20.27 and 24.82 µg/mL, respectively) and Klebsiella pneumoniae (IC50 = 43.21 and 94.4 µg/mL, respectively), compared with the standard meropenem (IC50 = 28.67 and 43.94 µg/mL, respectively). Compounds 3 and 5 showed antimalarial activity against Plasmodium falciparum D6 with IC50 values of 1.57 and 4.72 µg/mL and P. falciparum W2 with IC50 values of 0.61 and 2.91 µg/mL, respectively, compared with the standard chloroquine (IC50 = 0.026 and 0.14 µg/mL, respectively).

Aureanin: a new iridoid from the leaves of Tabebuia aurea (Silva Manso) Benth. & Hook.f. ex S.Moore.

One new iridoid named aureanin (1) was isolated from the leaves of Tabebuia aurea (Silva Manso) Benth. & Hook.f. ex S.Moore, together with eight known compounds, isoquercetin (2), astragalin (3), callicoside B (4), amphipaniculoside E (5), rehmaglutin D (6), quercetin-3-sambubioside (7), rutin (8), kaempferol-3-O-rutinoside (9). The structures of the isolated compounds were elucidated and confirmed by spectroscopic methods, including 1 D and 2 D NMR experiments, as well as HR-ESI-MS. Compounds 1-9 were evaluated for their in vitro cytotoxic activity against three human cancer cell lines (A549, HepG2, and MCF-7) and Leishmania major. Compound 4 showed activity against A549 (IC50: 36.8 ± 1.5 µg/mL, etoposide (positive control): 28.1 ± 4.2 µg/mL), however, none of the compounds were active against L. major.

Cytotoxic and antileishmanial triterpenes of Tabebuia aurea (Silva Manso) leaves.

The bioactivity-guided fractionation of the total ethanolic extract of the leaves of Tabebuia aurea revealed the cytotoxic and antileishmanial potency of the ethyl acetate fraction, in which its phytochemical investigation resulted in the isolation of five triterpenes; identified as oleanolic acid (1), ursolic acid (2), pomolic acid (3), tormentic acid (4), 3ß,6ß,19α-trihydroxy-urs-12-en-28-oic acid (5) in addition to one triterpenoid glucoside, spathodic acid 28-O-ß-D-glucopyranoside (6). Whereas compound 1 showed cytotoxic activity against three different cell lines; A549, MCF-7 and HepG2 with IC50 values of 31.7 ± 1.2, 27.4 ± 1.8 and 28.8 ± 1.1 µg/mL, respectively (etoposide as a positive control: 28.1 ± 4.2, 22.5 ± 4.5, and 20.4 ± 0.8 µg/mL, respectively), while compounds 1 and 2 showed antileishmanial activity with IC50 values of 10.2 ± 0.9 µg/mL and 5.1 ± 0.4 µg/mL, respectively (miltefosine: 7.7 ± 2.1 µg/mL).

NS3 helicase inhibitory potential of the marine sponge Spongia irregularis.

In the current study, an investigation of the activity of the total extract of the marine sponge Spongia irregularis and its different fractions against the hepatitis C virus (HCV) was pursued. The results revealed that the ethyl acetate fraction exhibited the highest anti-HCV activity, with an IC50 value of 12.6 ± 0.05 µg ml-1. Chromatographic resolution of the ethyl acetate fraction resulted in the isolation of four known compounds, 1,3,7-trimethylguanine (1), 3,5-dihydroxyfuran-2(5H)-one (2), thymidine (3), and 1H-indazole (4). By using LC-HR-ESI-MS metabolic profiling, compounds 5-14 were also identified in the same fraction. Molecular docking calculations revealed the high binding affinity of compound 14 against the allosteric pocket of HCV NS3-NS4A and the active site of HCV NS3 helicase (-10.1 and -7.4 kcal mol-1, respectively). Molecular dynamics simulations, followed by molecular mechanics-generalized Born surface area energy calculations, demonstrated the structural and energetic stability of compound 14 in complex with HCV targets.

The Red Sea marine sponge Spongia irregularis: metabolomic profiling and cytotoxic potential supported by in silico studies.

The current study discusses the chemical composition of the marine sponge Spongia irregularis using LC-HRESIMS. The metabolomic profiling resulted in the annotation of 17 metabolites of different chemical classes. Additionally, evaluation of the cytotoxic activities of the total extract and different fractions were carried out against three different cell lines where the n-butanol fraction exhibited the highest cytotoxic effects against HepG-2, MCF-7 and CACO-2 cell lines with IC50 values of 9.6 ± 0.02, 4.3 ± 0.10 and 5.6 ± 0.03 µg/mL, respectively. Also, the study was supported by docking study of the identified compounds for binding affinity to MSK1.

Cytotoxicity and chemical profiling of the Red Sea soft corals Litophyton arboreum.

The objective of this research was to evaluate the cytotoxic activities of the fractions and isolated compounds of the soft corals Litophyton arboreum against A549, MCF-7 and HepG2 cell lines by MTT assay method, and to chemically investigate the various metabolites of its total extract using LC-HR-ESI-MS metabolomic profiling. The metabolomic profiling revealed the presence of various metabolites, mainly sesquiterpenes and steroids reported for the first time in L. arboreum. Additionally, eight compounds (1-8) have been isolated from the n-hexane-chloroform (1:1) fraction that exhibited noticeable activity towards A549, MCF-7 and HepG2 cell lines. The steroids (5 and 6), and the sesquiterpene (1) exerted noticeable activity against A549 cell line (IC50 28.5 ± 4.4, 36.9 ± 2.9 and 67.3 ± 9.9 µM/mL, respectively) compared to etoposide as standard cytotoxic agent (IC50 48.3 ± 7.6 µM/mL). Compound 6 also exhibited cytotoxicity against MCF-7 cell line (IC50 55.3 ± 4.9 µM/mL).

Elastase inhibitory activity of secondary metabolites from the fungus Virgaria nigra CF-231658.

Three known compounds were isolated from Virgaria nigra CF-231658; 2,7-dihydroxy naphthalene (1), virgaricin B (2) and virgaricin (3). The isolated compounds was obtained from liquid-state and agar-supported fermentation using Amberlite XAD-16 solid-phase extraction during the cultivation step. Their structures were elucidated on the basis of 1D and 2D NMR as well as HRMS spectroscopic analyses. The isolated compounds were examined for their ability to inhibit elastase using normal human diploid fibroblasts. Compound 2 displayed the most potent activity with 76.7 ± 2.12% inhibition of the enzyme activity at 5 µM concentration.

LC-MS-based identification of bioactive compounds and hepatoprotective and nephroprotective activities of Bignonia binata leaves against carbon tetrachloride-induced injury in rats.

The chemical profiling of the main phytoconstituents of total ethanolic extract (TEE) and its different fractions of Bignonia binata leaves was dereplicated using liquid chromatography-high resolution-electrospray ionisation-mass spectrometry (LC-HR-ESI-MS), revealed the presence of various classes of secondary metabolites; eight phenylethanoids, two flavonoidal glycosides and two iridoids. Moreover, the hepatoprotective and nephroprotective activities of the TEE and its different fractions were investigated in carbon tetrachloride (CCl4)-intoxicated rats and were compared with those of silymarin-treated group, revealing the highest potency of the EtOAc group, followed by the aqueous one in improving the CCl4-induced alterations in several biochemical parameters. Besides, EtOAc and aqueous fractions exhibited the most inhibition of CCl4-induced inflammatory mediators and improving the changes in the histopathological structures of the liver and kidney. In addition, the EtOAc fraction demonstrated the highest total phenolic content, whereas TEE showed the highest amount of total flavonoid content.[Formula: see text].

Recent Updates on Sinularia Soft Coral.

Marine organisms are recognized as a rich source of bioactive secondary metabolites. The remarkable abundance and diversity of bioactive small molecules isolated from soft corals displayed their essential role in drug discovery for human diseases. Sterols and terpenes, particularly cembranolides, 14-membered cyclic diterpene, demonstrated numerous biological activities, such as antitumor, antimicrobial, antiviral, antidiabetic, anti-osteoporosis and anti-inflammatory. Accordingly, continuous investigation of marine soft corals leads the way to discover a plentiful number of chemical diverse natural products with various biological potentials for prospective pharmaceutical industrial applications. Such review affords plenary inspection of the total secondary metabolites isolated from the Sinularia, from 2008 until 2020, besides their natural sources as well as bioactivities whenever possible.

Gas chromatography-mass spectrometry profiling and analgesic, anti-inflammatory, antipyretic, and antihyperglycemic potentials of Persea americana.

OBJECTIVES: The present study determines the chemical constituents of Persea americana using gas chromatography-mass spectrometry (GC-MS) and its different activities. MATERIALS AND METHODS: Air-dried powdered leaves of Persea americana were extracted by 95% methanol and fractionated consecutively with petroleum ether, chloroform, and ethyl acetate. The saponifiable matter, EtOAc and aqueous fractions were subjected to GC-MS. The analgesic, anti-inflammatory, antipyretic, and antihyperglycemic properties of extracts, different fractions, and crude polysaccharide were determined by hot plate, carrageenan-induced paw edema, yeast-induced pyrexia, and alloxan-induced hyperglycemia methods, respectively. RESULTS: Fourteen fatty acid methyl esters were identified in GC-MS-based profiling of the saponifiable matter. Alongside, 13 compounds were determined from EtOAc fraction and 6 compounds from the aqueous fraction of P. americana leaves. The ethyl acetate fraction and total stem extract displayed high anti-inflammatory potential with percentage of paw edema reduction by 48.99 and 47.54 %, respectively, compared with that of indomethacin (42.90 %). The ethyl acetate fraction and total stem extract revealed the highest analgesic activity with 137.95 and 137.12 % percent of protection against external stimulus, respectively. Investigation of antipyretic efficiency showed the total stem extract and crude polysaccharides attained normal temperature after 3 hr, which was very close to that of acetylsalicylic acid. The total leaf and stem extracts displayed significant antihyperglycemic activity with significant reduction in the level of blood glucose by 76.67 and 59.05 %, respectively. CONCLUSION: P. americana had analgesic, anti-inflammatory, antipyretic, and antihyperglycemic properties, which refer to its bioactive metabolites.

NS3/4A helicase inhibitory alkaloids from Aptenia cordifolia as HCV target.

Chemical investigation of Aptenia cordifolia roots extract, using chromatographic and spectroscopic techniques, resulted in isolation and identification of eight known compounds. The basic ethyl acetate fraction (alkaloidal fraction) afforded O-methylsceletenone, epinine, 4-methoxy phenethylamine, and N-methyl tyramine while, the acidic ethyl acetate fraction (non-alkaloidal fraction) afforded only cis-N-coumaroyl tyramine. Moreover, the petroleum ether fraction afforded capric acid, tricosanol, and a mixture of ß-sitosterol & stigma sterol. Upon screening of anti HCV activity of these three fractions, only the basic ethyl acetate fraction had high activity against HCV with an IC50 value equal to 2.4 µg mL-1 which provoked us to carry out structure based in silico virtual screening on the drug targets of HCV of isolated alkaloidal compounds as well as the previously dereplicated alkaloids through metabolomics from the antiviral active fraction. The tortuosamine compound exhibited the strongest binding to the active site of NS3/4A helicase with a binding affinity (-7.1 kcal mol-1) which is very close to the native ligand (-7.7 kcal mol-1).

Metabolomic profiling and biological investigation of Tabebuia Aurea (Silva Manso) leaves, family Bignoniaceae.

Both ethyl acetate and aqueous fractions of Tabebuia aurea leaves exhibited noteworthy antioxidant and nephroprotective activities against carbon tetrachloride (CCl4)-induced nephrotoxicity in rats, as evidenced by the remarkable improvements of renal serum biomarkers and histopathological features. Additionally, the ethyl acetate fraction displayed a prominent in vitro antitrypanosomal activity against Trypanosoma brucei; consequently, the leaves were subjected to LC-HR-ESI-MS metabolomic profiling to discover the constituents that possibly underlie their bioactivities. Therefore, ten metabolites were characterized, mostly dominated by flavonoids. Interestingly, two identified constituents viz., 3,9,12,15-octadecatetraenoic acid (9) and 9,11,13-octadecatrienoic acid (10) are reported firstly herein from the genus Tabebuia. Furthermore, among the dereplicated constituents, rutin (5) and kaempferol 3-O-rutinoside (6) exhibited the highest docking scores as effective antitrypanosomal compounds.

Metabolomic profiling and anti-infective potential of Zinnia elegans and Gazania rigens (Family Asteraceae).

The present study evaluates the chemical composition of Zinnia elegans and Gazania rigens based on their metabolomic profiles using liquid chromatography coupled with high-resolution mass spectrometry (LC-HR-MS), alongside with the anti-infective activities of their ethanol extracts, as well as, different fractions. A significant difference was observed between the LC-MS profiles of the two plants such as, coumarins, sesquiterpene lactones and phenylethanoids which were characteristic for Z. elegans, while amides and phenolic acid derivatives were characteristic for G. rigens. These results highlight the chemical potential of Z. elegans and G. rigens. Furthermore, the ethyl acetate fraction of Z. elegans showed a significant antimalarial activity with IC50 values of 21.03 and 13.72 µg/mL against Plasmodium falciparum D6 and P. falciparum W2, respectively.