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.

Evaluation of the anti-infective potential of the seed endophytic fungi of Corchorus olitorius through metabolomics and molecular docking approach.

BACKGROUND: Endophytic fungi are very rich sources of natural antibacterial and antifungal compounds. The main aim of this study is to isolate the fungal endophytes from the medicinal plant Corchorus olitorius seeds (F. Malvaceae), followed by antimicrobial screening against various bacterial and fungal strains. RESULTS: Seven endophytic fungal strains belonging to different three genera were isolated, including Penicillium, Fusarium, and Aspergillus. The seven isolated endophytic strains revealed selective noticeable activity against Escherichia coli (ATCC25922) with varied IC50s ranging from 1.19 to 10 µg /mL, in which Aspergillus sp. (Ar 6) exhibited the strongest potency against E. coli (ATCC 25,922) and candida albicans (ATCC 10,231) with IC50s 1.19 and 15 µg /mL, respectively. Therefore, the chemical profiling of Aspergillus sp. (Ar 6) crude extract was performed using LC-HR-ESI-MS and led to the dereplication of sixteen compounds of various classes (1-16). In-silico analysis of the dereplicated metabolites led to highlighting the compounds responsible for the antimicrobial activity of Aspergillus sp. extract. Moreover, molecular docking showed the potential targets of the metabolites; Astellatol (5), Aspergillipeptide A (10), and Emericellamide C (14) against E. coli and C. albicans. CONCLUSION: These results will expand the knowledge of endophytes and provide us with new approaches to face the global antibiotic resistance problem and the future production of undiscovered compounds different from the antibiotics classes.

Paralemnalia thyrsoides-associated fungi: phylogenetic diversity, cytotoxic potential, metabolomic profiling and docking analysis.

BACKGROUND: Cancer continues to be one of the biggest causes of death that affects human health. Chemical resistance is still a problem in conventional cancer treatments. Fortunately, numerous natural compounds originating from different microbes, including fungi, possess cytotoxic characteristics that are now well known. This study aims to investigate the anticancer prospects of five fungal strains that were cultivated and isolated from the Red Sea soft coral Paralemnalia thyrsoides. The in vitro cytotoxic potential of the ethyl acetate extracts of the different five isolates were evaluated using MTS assay against four cancer cell lines; A549, CT-26, MDA-MB-231, and U87. Metabolomics profiling of the different extracts using LC-HR-ESI-MS, besides molecular docking studies for the dereplicated compounds were performed to unveil the chemical profile and the cytotoxic mechanism of the soft coral associated fungi. RESULTS: The five isolated fungal strains were identified as Penicillium griseofulvum (RD1), Cladosporium sphaerospermum (RD2), Cladosporium liminiforme (RD3), Penicillium chrysogenum (RD4), and Epicoccum nigrum (RD5). The in vitro study showed that the ethyl acetate extract of RD4 exhibited the strongest cytotoxic potency against three cancer cell lines A549, CT-26 and MDA-MB-231 with IC50 values of 1.45 ± 8.54, 1.58 ± 6.55 and 1.39 ± 2.0 µg/mL, respectively, also, RD3 revealed selective cytotoxic potency against A549 with IC50 value of 6.99 ± 3.47 µg/mL. Docking study of 32 compounds dereplicated from the metabolomics profiling demonstrated a promising binding conformation with EGFR tyrosine kinase that resembled its co-crystallized ligand albeit with better binding energy score. CONCLUSION: Our results highlight the importance of soft coral-associated fungi as a promising source for anticancer metabolites for future drug discovery.

The endophytic Fusarium strains: a treasure trove of natural products.

The complexity and structural diversity of the secondary metabolites produced by endophytes make them an attractive source of natural products with novel structures that can help in treating life-changing diseases. The genus Fusarium is one of the most abundant endophytic fungal genera, comprising about 70 species characterized by extraordinary discrepancy in terms of genetics and ability to grow on a wide range of substrates, affecting not only their biology and interaction with their surrounding organisms, but also their secondary metabolism. Members of the genus Fusarium are a source of secondary metabolites with structural and chemical diversity and reported to exhibit diverse pharmacological activities. This comprehensive review focuses on the secondary metabolites isolated from different endophytic Fusarium species along with their various biological activities, reported in the period from April 1999 to April 2022.

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).

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].

Bioactive natural products from marine sponges belonging to family Hymedesmiidae.

Natural products of marine origin exhibit extensive biological activities, and display a vital role in the exploration of new compounds for drug development. Marine sponges have been reported at the top with respect to the discovery of biologically active metabolites that have potential pharmaceutical applications. The family Hymedesmiidae belonging to the Demospongiae class includes ten accepted genera, of which four genera were explored for their bioactive metabolites, namely Phorbas, Hamigera, Hemimycale, and Kirkpatrickia. Genus Phorbas has received more attention due to the isolation of various classes of compounds with unique structures mainly diterpenes, alkaloids, sesterterpenes, and steroids that exhibited diverse biological activities including: antiviral, antimicrobial, and anti-inflammatory, whereas anticancer compounds predominated. This review focuses on the isolated secondary metabolites from family Hymedesmiidae with their biological potential and covers the literature from 1989 to 2020.

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.

Antiproliferative activity of new pentacyclic triterpene and a saponin from Gladiolus segetum Ker-Gawl corms supported by molecular docking study.

A new triterpenoidal saponin identified as 3-O-[ß-d-glucopyranosyl-(1 → 2)-ß-d-glucopyranosyl-(1 → 4)-ß-d-xylopyranosyl]-2ß,3ß,16α-trihydroxyolean-12-en-23,28-dioic acid-28-O-α-l-rhamnopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-ß-d-glucopyranosyl-(1 → 2)-α-l-arabinopyranoside 1 together with a new oleanane triterpene identified as 2ß,3ß,13α,22α-tetrahydroxy olean-23,28-dioic acid 2 and 6 known compounds (3-8) have been isolated from Gladiolus segetum Ker-Gawl corms. The structural elucidation of the isolated compounds was confirmed using different chemical and spectroscopic methods, including 1D and 2D NMR experiments as well as HR-ESI-MS. Moreover, the in vitro cytotoxic activity of the fractions and that of the isolated compounds 1-8 were investigated against five human cancer cell lines (PC-3, A-549, HePG-2, MCF-7 and HCT-116) using doxorubicin as a reference drug. The results showed that the saponin fraction exhibited potent in vitro cytotoxic activity against the five human cancer cell lines, whereas the maximum activity was exhibited against the PC-3 and A-549 cell lines with the IC50 values of 1.13 and 1.98 µg mL-1, respectively. In addition, compound 1 exhibited potent activity against A-549 and PC-3 with the IC50 values of 2.41 µg mL-1 and 3.45 µg mL-1, respectively. Interestingly, compound 2 showed the maximum activity against PC-3 with an IC50 of 2.01 µg mL-1. These biological results were in harmony with that of the molecular modeling study, which showed that the cytotoxic activity of compound 2 might occur through the inhibition of the HER-2 enzyme.