Zygo-Albuside A: New Saponin from Zygophyllum album L. with Significant Antioxidant, Anti-Inflammatory and Antiapoptotic Effects against Methotrexate-Induced Testicular Damage.

Chemical investigation of the crude extract of the aerial part of Zygophyllum album L. (Z. album) led to the isolation of a new saponin, Zygo-albuside A (7), together with seven known compounds, one of them (caffeic acid, compound 4) is reported in the genus for the first time. NMR (1D and 2D) and mass spectrometric analysis, including high-resolution mass spectrometry (HRMS), were utilized to set up the chemical structures of these compounds. The present biological study aimed to investigate the protective antioxidant, anti-inflammatory, and antiapoptotic activities of the crude extract from the aerial part of Z. album and two of its isolated compounds, rutin and the new saponin zygo-albuside A, against methotrexate (MTX)-induced testicular injury, considering the role of miRNA-29a. In all groups except for the normal control group, which received a mixture of distilled water and DMSO (2:1) as vehicle orally every day for ten days, testicular damage was induced on the fifth day by intraperitoneal administration of MTX at a single dose of 20 mg/kg. Histopathological examination showed that pre-treatment with the crude extract of Z. album, zygo-albuside A, or rutin reversed the testicular damage induced by MTX. In addition, biochemical analysis in the protected groups showed a decrease in malondialdehyde (MDA), interleukin-6 (IL-6) and IL-1ß, Bcl-2-associated-protein (Bax), and an increase in B-cell lymphoma 2 (Bcl-2) protein, catalase (CAT), superoxide dismutase (SOD) in the testis, along with an increase in serum testosterone levels compared with the unprotected (positive control) group. The mRNA expression levels of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), p53, and miRNA-29a were downregulated in the testicular tissues of the protected groups compared with the unprotected group. In conclusion, the study provides sufficient evidence that Z. album extract, and its isolated compounds, zygo-albuside A and rutin, could alleviate testicular damage caused by the chemotherapeutic agent MTX.

Silver Nanoparticles Formulation of Flower Head's Polyphenols of Cynara scolymus L.: A Promising Candidate against Prostate (PC-3) Cancer Cell Line through Apoptosis Activation.

Cynara scolymus L. (Family: Compositae) or artichoke is a nutritious edible plant widely used for its hepatoprotective effect. Crude extracts of flower, bract, and stem were prepared and evaluated for their in vitro antioxidant activity and phenolic content. The flower crude extract exhibited the highest phenolic content (74.29 mg GAE/gm) as well as the best in vitro antioxidant activity using total antioxidant capacity (TAC), ferric reducing antioxidant power (FEAP), and 1,1-diphenyl-2-picrylhyazyl (DPPH) scavenging assays compared with ascorbic acid. Phenolic fractions of the crude extracts of different parts were separated and identified using high-performance liquid chromatography HPLC-DAD analysis. The silver nanoparticles of these phenolic fractions were established and tested for their cytotoxicity and apoptotic activity. Results showed that silver nanoparticles of a polyphenolic fraction of flower extract (Nano-TP/Flowers) exhibited potent cytotoxicity against prostate (PC-3) and lung (A549) cancer cell lines with IC50 values of 0.85 µg/mL and 0.94 µg/mL, respectively, compared with doxorubicin as a standard. For apoptosis-induction, Nano-TP/Flowers exhibited apoptosis in PC-3 with a higher ratio than in A549 cells. It induced total prostate apoptotic cell death by 227-fold change while it induced apoptosis in A549 cells by 15.6-fold change. Nano-TP/Flowers upregulated both pro-apoptotic markers and downregulated the antiapoptotic genes using RT-PCR. Hence, this extract may serve as a promising source for anti-prostate cancer candidates.

GC-MS/MS Quantification of EGFR Inhibitors, ß-Sitosterol, Betulinic Acid, (+) Eriodictyol, (+) Epipinoresinol, and Secoisolariciresinol, in Crude Extract and Ethyl Acetate Fraction of Thonningia sanguinea.

Medicinal plants are widely used in folk medicine to treat various diseases. Thonningia sanguinea Vahl is widespread in African traditional medicine, and exhibits antioxidant, antibacterial, antiviral, and anticancer activities. T. sanguinea is a source of phytomedicinal agents that have previously been isolated and structurally elucidated. Herein, gas chromatography combined with tandem mass spectrometry (GC-MS/MS) was used to quantify epipinoresinol, ß-sitosterol, eriodictyol, betulinic acid, and secoisolariciresinol contents in the methanolic crude extract and its ethyl acetate fraction for the first time. The ethyl acetate fraction was rich in epipinoresinol, eriodictyol, and secoisolariciresinol at concentrations of 2.3, 3.9, and 2.4 mg/g of dry extract, respectively. The binding interactions of these compounds with the epidermal growth factor receptor (EGFR) were computed using a molecular docking study. The results revealed that the highest binding affinities for the EGFR signaling pathway were attributed to eriodictyol and secoisolariciresinol, with good binding energies of -19.93 and -16.63 Kcal/mol, respectively. These compounds formed good interactions with the key amino acid Met 769 as the co-crystallized ligand. So, the ethyl acetate fraction of T. sanguinea is a promising adjuvant therapy in cancer treatments.

Chemical Constituent Profiling of Phyllostachys heterocycla var. Pubescens with Selective Cytotoxic Polar Fraction through EGFR Inhibition in HepG2 Cells.

Different extracts of the Bamboo shoot skin Phyllostachys heterocycla var. pubescens were screened against panel of cancer cell lines and normal one. The cell viability results exhibited that the ethyl acetate extract showed the least vitality percentage of 2.14% of HepG2 cells. Accordingly, it was subjected to chromatographic separation, which resulted in the isolation of a new natural product; 7-hydroxy, 5-methoxy, methyl cinnamate (1), together with four known compounds. The structures of the pure isolated compounds were deduced based on different spectroscopic data. The new compound (1) was screened against the HepG2 and MCF-7 cells and showed IC50 values of 7.43 and 10.65 µM, respectively. It induced apoptotic cell death in HepG2 with total apoptotic cell death of 58.6% (12.44-fold) compared to 4.71% in control by arresting cell cycle progression at the G1 phase. Finally, compound 1 was validated as EGFR tyrosine kinase inhibitor in both enzymatic levels (IC50 = 98.65 nM compared to Erlotinib (IC50 = 78.65 nM). Finally, in silico studies of compound 1 through the molecular docking indicated its high binding affinity towards EGFR protein and the ADME pharmacokinetics indicated it as a drug-like.

Cytotoxic, Apoptosis-Inducing Activities, and Molecular Docking of a New Sterol from Bamboo Shoot Skin Phyllostachys heterocycla var. pubescens.

Phytochemical screening of nonpolar fractions from the methanol extract of the Bamboo shoot skin Phyllostachys heterocycla var. pubescens resulted in the isolation of a new sterol-glucoside-fatty acid derivative (6'-O-octadeca-8'',11''-dienoyl)-sitosterol-3-O-ß-d-glucoside (1), together with six known compounds. The chemical structures of the pure isolated compounds were deduced based on different spectral data. The isolated compounds were assessed to determine their cytotoxic activity, and the results were confirmed by determining their apoptotic activity. Compound 1 was more cytotoxic against the MCF-7 cells (IC50 = 25.8 µM) compared to Fluorouracil (5-FU) (26.98 µM), and it significantly stimulated apoptotic breast cancer cell death with 32.6-fold (16.63% compared to 0.51 for the control) at pre-G1 and G2/M-phase cell cycle arrest and blocked the progression of MCF-7 cells. Additionally, RT-PCR results further confirmed the apoptotic activity of compound 1 by the upregulation of proapoptotic genes (P53; Bax; and caspases 3, 8, and 9) and downregulation of the antiapoptotic genes (BCL2). Finally, the identified compounds, especially 1, were found to have high binding affinity towards both tyrosine-specific protein kinase (TPK) and vascular endothelial growth factor receptor (VEGFR-2) through the molecular docking studies that highlight its mode of action.

Bioactive Diketopiperazines and Nucleoside Derivatives from a Sponge-Derived Streptomyces Species.

Fractionation and purification of the ethyl acetate extract of the culture of a sponge-derived actinomycete, Streptomyces species Call-36, resulted in the isolation and identification of a new diketopiperazine, actinozine A (1), cyclo(2-OH-d-Pro-l-Leu) (2), two new nucleosides, thymidine-3-mercaptocarbamic acid (3) and thymidine-3-thioamine (4), together with cyclo(d-Pro-l-Phe) (5) and cyclo(l-Pro-l-Phe) (6). The structure assignments of the compounds were carried out by interpretation of 1D and 2D NMR data and mass spectral determinations. The absolute configurations of 1 and 2 were determined by Marfey's method and by comparison of the experimental and TDDFT-calculated ECD spectra. Actinozine A possesses an unprecedented hydroperoxy moiety at C-2 of the proline moiety, while 3 and 4 possess unusual mercaptocarbamic acid and thiohydroxylamine functionalities at N-3 of the thymine moiety. The isolated compounds displayed variable cytotoxic and antimicrobial activities.

Plicosepalin A, a new antioxidant catechin-gallic acid derivative of inositol from the mistletoe Plicosepalus curviflorus.

Phytochemical investigation of the semi-parasitic plant, Plicosepalus curviflorus (Loranthaceae) growing in Saudi Arabia resulted in the isolation of a new catechin-gallic acid derivative of inositol, plicosepalin A (1) [(+) catechin-4'-O-(1″-O-galloyl-5″-O-methyl)-myo-inositol], along with seven known compounds: methyl gallate (2), catechin (3), quercetin (4), gallic acid (5), lupeol (6), ß-sitosterol (7), and ursolic acid (8). Their structures were elucidated on the basis of spectroscopic analyses, including HRESIMS, ESIMS, 1H and 13C NMR, HSQC, and HMBC, as well as comparison with reported data. The antioxidant and antimicrobial activities of 1 were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the disc diffusion assay, respectively. Compound 1 exhibited potent free radical scavenging activity with an IC50 value of 9.0 ± 0.27 µM. Moreover, significant activities against Staphylococcus aureus and Bacillus subtilis were recorded.

Penicilloitins A and B, new antimicrobial fatty acid esters from a marine endophytic Penicillium species.

Two new antimicrobial fatty acid esters, penicilloitins A and B (1 and 2), along with α-cyclopiazonic acid (3), tryptamine (4) and indole-3-carbaldehyde (5), were isolated from mycelial extracts and the culture broth of a marine endophytic Penicillium species and their structures established by spectroscopic techniques including 1D (1H NMR and 13C NMR) and 2D NMR (COSY, multiplicity-edited HSQC, and HMBC) as well as HRESIMS. Of these compounds, 1, 3 and 4 displayed modest antimicrobial activity.

Bioactive 2(1H)-Pyrazinones and Diketopiperazine Alkaloids from a Tunicate-Derived Actinomycete Streptomyces sp.

As a part of our ongoing effort to allocate marine microbial bioactive leads, a tunicate-derived actinomycete, Streptomyces sp. Did-27, was investigated. Three new 2(1H)-pyrazinones derivatives, (S)-6-(sec-butyl)-3-isopropylpyrazin-2(1H)-one (1), (S)-3-(sec-butyl)-6-isopropylpyrazin-2(1H)-one (2) and (S)-6-(sec-butyl)-3-isobutylpyrazin-2(1H)-one (3), together with the known (1H)-pyrazinones analogues deoxymutaaspergillic acid (4), 3,6-diisobutyl-2(1H)-pyrazinone (5) and 3,6-di-sec-butyl-2(1H)-pyrazinone (6), and the diketopiperazine alkaloids cyclo(6-OH-d-Pro-l-Phe) (7), bacillusamide B (8), cyclo(l-Pro-l-Leu) and cyclo(l-Pro-l-Ile) (10) were isolated from this strain. The structures of the compounds were determined by study of their one- and two-dimensional NMR spectra as well as high-resolution mass spectral determinations. Compound 4 was reported previously as a synthetic product, while compound 6 was reported as 2-hydroxy-3,6-di-sec-butylpyrazine. Herein, we report the complete NMR data for compounds 4 and 6. The compounds were evaluated for their cytotoxic activities against three cell lines. Compound 5 showed potent and selective activity against HCT-116 cell line with IC50 of 1.5 µg/mL, while 1-10 showed variable cytotoxic activities against these cancer cell lines. These results provide further understanding about the chemistry and bioactivities of the alkylated 2(1H)-pyrazinone derivatives.

Bioactive secondary metabolites from the Red Sea marine Verongid sponge Suberea species.

In a continuation of our efforts to identify bioactive compounds from Red Sea Verongid sponges, the organic extract of the sponge Suberea species afforded seven compounds including two new dibrominated alkaloids, subereamollines C and D (1 and 2), together with the known compounds aerothionin (3), homoaerothionin (4), aeroplysinin-1 (5), aeroplysinin-2 (6) and a revised subereaphenol C (7) as ethyl 2-(2,4-dibromo-3,6-dihydroxyphenyl)acetate. The structures of the isolated compounds were assigned by different spectral data including optical rotations, 1D (1H and 13C) and 2D (COSY, multiplicity-edited HSQC, and HMBC) NMR and high-resolution mass spectroscopy. Aerothionin (3) and subereaphenol C (7) displayed potent cytotoxic activity against HeLa cell line with IC50 values of 29 and 13.3 µM, respectively. In addition, aeroplysinin-2 (6) showed potent antimigratory activity against the human breast cancer cell line MDA-MB-231 with IC50 of 18 µM. Subereamollines C and D are new congeners of the previously reported compounds subereamollines A and B with methyl ester functionalities on the side chain. These findings provide further insight into the biosynthetic capabilities of members of the genus Suberea and the chemical diversity as well as the biological activity of these compounds.

Prevalence and antimicrobial resistance profile of Staphylococcus species in chicken and beef raw meat in Egypt.

Coagulase-positive (CPS) and coagulase-negative (CNS) staphylococci cause staphylococcal food poisoning. Recently, CPS and CNS have received increasing attention due to their potential role in the dissemination of antibiotic resistance markers. The present study aimed to evaluate CPS and CNS species distribution and their antibiotic resistance profile isolated from chicken and beef meat. Fifty fresh, uncooked chicken parts and 50 beef meat cuts (local n=27; imported n=23) were used. One hundred staphylococcal isolates belonging to 11 species were isolated and identified from chicken (n=50) and beef (n=50) raw meat samples. Staphylococcus hyicus (26/100), lugdunensis (18/100), aureus (15/100) and epidermidis (14/100) were dominant. S. aureus was 100% resistant to penicillin and sulfamethoxazole/trimethoprim. Vancomycin-resistant S. aureus showed intermediate resistance (51%), which might indicate the dissemination of vancomycin resistance in the community and imply food safety hazards. The percentage of resistance to ß-lactams was variable, with the highest resistance being to penicillin (94%) and lowest to ampicillin-sulbactam (22%). Antimicrobial resistance was mainly against penicillin (94%), clindamycin (90%) and sulfamethoxazole/trimethoprim (82%). The results indicate that chicken and beef raw meat are an important source of antibiotic-resistant CPS and CNS.

Didemnaketals f and g, new bioactive spiroketals from a red sea ascidian didemnum species.

In continuation of our ongoing efforts to identify bioactive compounds from Red Sea marine organisms, a new collection of the ascidian Didemnum species was investigated. Chromatographic fractionation and HPLC purification of the CH2Cl2 fraction of an organic extract of the ascidian resulted in the identification of two new spiroketals, didemnaketals F (1) and G (2). The structure determination of the compounds was completed by extensive study of 1D (1H, 13C, and DEPT) and 2D (COSY, HSQC, and HMBC) NMR experiments in addition to high-resolution mass spectral data. Didemnaketal F (1) and G (2) differ from the previously reported compounds of this class by the lack the terminal methyl ester at C-1 and the methyl functionality at C-2. Instead, 1 and 2 possess a methyl ketone moiety instead of the terminal ester. Furthermore, didemnaketal F possesses a disubstituted double bond between C-2 and C-3, while the double bond was replaced by a secondary alcohol at C-3 in didemnaketal G. In addition, they possess the unique spiroketal/hemiketal functionality which was previously reported in didemnaketal E. Didemnaketals F (1) and G (2) displayed moderate activity against HeLa cells with of IC50s of 49.9 and 14.0 µM, respectively. In addition, didemnaketal F (1) displayed potent antimicrobial activity against E. coli and C. albicans. These findings provide further insight into the biosynthetic capabilities of this ascidian and the chemical diversity as well as the biological activity of this class of compounds.

Theonellamide G, a potent antifungal and cytotoxic bicyclic glycopeptide from the Red Sea marine sponge Theonella swinhoei.

In our search for bioactive metabolites from marine organisms, we have investigated the polar fraction of the organic extract of the Red Sea sponge Theonella swinhoei. Successive chromatographic separations and final HPLC purification of the potent antifungal fraction afforded a new bicyclic glycopeptide, theonellamide G. The structure of the peptide was determined using extensive 1D and 2D NMR and high-resolution mass spectral determinations. The absolute configuration of theonellamide G was determined by chemical degradation and 2D NMR spectroscopy. Theonellamide G showed potent antifungal activity towards wild and amphotericin B-resistant strains of Candida albicans with IC50 of 4.49 and 2.0 µM, respectively. Additionally, it displayed cytotoxic activity against the human colon adenocarcinoma cell line (HCT-16) with IC50 of 6.0 µM. These findings provide further insight into the chemical diversity and biological activities of this class of compounds.

Antihyperglycemic activities of extracts of the mistletoes Plicosepalus acaciae and P. curviflorus in comparison to their solid lipid nanoparticle suspension formulations.

The antihyperglycemic activity of the extracts and preparations of solid lipid nanoparticle suspensions of two mistletoes growing in Saudi Arabia, Plicosepalus acaciae and P. curviflorus, as well as their possible antioxidant effect were investigated in a type 2 diabetic animal model. Type 2 diabetes was induced in adult male Wistar rats by a high-fat diet followed by injection of streptozotocin (STZ). The diabetic rats were treated in parallel with pioglitazone hydrochloride (PIO), non-toxic extracts of P. acaciae and P. curviflorus, as well as three different solid lipid nanoparticle (SLN) suspension formulations prepared from each of the two extracts. Blood glucose level, insulin resistance, oxidative stress parameters, and antioxidant markers were determined. The total extracts of P. acaciae and P. curviflorus as well as the SLN formulations exhibited a significant blood glucose-lowering effect associated with antioxidant effects in the diabetic rats. The SLN preparation with the highest lipid content gave the best result. Reduction of hyperglycemia and insulin resistance in the diabetic rats was, at least partly, due to the antioxidant activities of the extracts and their SLN formulations.

Antioxidant and anti-inflammatory effects of Marrubium alysson extracts in high cholesterol-fed rabbits.

The antioxidant and anti-inflammatory effects of hexane (HEXA), chloroform (CHLORO), ethyl acetate (EA) and total alcoholic (T. ALCOH) extracts of Marrubium alysson in hypercholesterolemic-fed rabbits were evaluated. Hypercholesterolemia was induced in male rabbits by high cholesterol diet (HCD) (350 mg/kg) for 8 weeks. Hypercholesterolemic rabbits were allocated into groups, treated with simvastatin (SIM 5 mg/kg), different extracts of M. alysson at two doses of 250, 500 mg/kg. A normal control group and an HCD control one were used for comparison. Lipid profile, as well as oxidized low density lipoprotein-cholesterol (ox-LDL-C), myeloperoxidase activity (MPO) and superoxide anion production (O2•(-)), C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) were also evaluated. In addition, histological examination of ascending aorta was performed. We found dyslipidemia associated with significant increases in ox-LDL-C 123.5 ± 9.8 nmol MDA/mg non-HDL, MPO activity 0.08 ± 0.05 U/100 mg tissue and O2•(-) production 3.5 ± 0.3 nmol cytochrome C reduced/min/g tissue × 10(-4) in hypercholerterolemic rabbits. In addition, there was a significant increase in CRP 6.6 ± 0.49 µmol/L and MCP-1 190.9 ± 6.4 pg/ml and its mRNA expression in HCD. Intima appeared thick with thick plaques surrounding the intima and luminal narrowing. SIM, EA and HEXA extracts of M. alysson had lipid lowering effect, decrease in ox-LDL-C, MPO, O2•(-), CRP and MCP-1 mRNA expression with improvement of the pathological picture. M. alysson enhanced the stability of plaque, had lipid lowering, anti-inflammatory and antioxidant activities.

Metabolomic Profiling and In Vivo Antiepileptic Effect of Zygophyllum album Aerial Parts and Roots Crude Extracts against Pentylenetetrazole-Induced Kindling in Mice.

The chemical profiles of both Zygophyllum album (Z. album) aerial parts and roots extracts were evaluated with LC-ESI-TOF-MS/MS analysis. Twenty-four compounds were detected. Among them, some are detected in both the aerial parts and the roots extracts, and others were detected in the aerial parts only. The detected compounds were mainly flavonoids, phenolic compounds, triterpenes and other miscellaneous compounds. Such compounds contribute to the diverse pharmacological activities elicited by the Z. album species. This study aimed to elucidate the antiepileptic effect of Z. album aerial parts and roots crude extracts against pentylenetetrazole (PTZ)-induced kindling in mice. Male albino mice were divided into four groups, eight animals each. All groups, except the control group, were kindled with PTZ (35 mg/kg i.p.), once every alternate day for a total of 15 injections. One group was left untreated (PTZ group). The remaining two groups were treated prior to PTZ injection with either Z. album aerial parts or roots crude extract (400 mg/kg, orally). Pretreatment with either extract significantly reduced the seizure scores, partially reversed the histological changes in the cerebral cortex and exerted antioxidant/anti-inflammatory efficacy evinced by elevated hippocampal total antioxidant capacity and SOD and catalase activities, parallel to the decrement in MDA content, iNOS activity and the TXNIB/NLRP3 axis with a subsequent decrease in caspase 1 activation and a release of IL-1ß and IL-18. Moreover, both Z. album extracts suppressed neuronal apoptosis via upregulating Bcl-2 expression and downregulating that of Bax, indicating their neuroprotective and antiepileptic potential. Importantly, the aerial parts extract elicited much more antiepileptic potential than the roots extract did.

A UPLC- MS/MS Method to Quantify ß-Sitosterol and Ferulic Acid of Pygeum Africanum Extract in Bulk and Pharmaceutical Preparation.

This study uses a liquid chromatography-electrospray ionization-tandem mass spectrometry method to determine ß-Sitosterol and Ferulic acid in Pygeum africanum extract. Chromatographic separation of the two analytes was performed on an ACQUITY UPLC H-Class system coupled with Xevo TQD mass spectrometer and HSS T3 C18 column (2.1 X 50 mm, 1.8 µm). Mobile phase A consisted of an aqueous solution of 0.1% formic acid (v/v), and mobile phase B was 0.1% formic acid (v/v) in methanol pumped through a gradient elution mode. Mass spectrometer parameters were optimized using an electrospray ionization source in the positive and negative ionization modes. The quantification of the two analytes was performed using multiple reaction monitoring transitions. The method was fully validated per (FDA) guidelines regarding linearity, accuracy, precision, carryover and selectivity. The proposed method was applied successfully to determine the two investigated compounds in commercially available pharmaceutical products.

Silver nanoparticles formulation of Marrubium alysson L. phenolic extract potentiates cytotoxicity through apoptosis with molecular docking study as Bcl-2 inhibitors.

Crude or semi-purified extracts of plants can play a significant role as antitumor agents. They were used as stabilizing and reducing agents in the preparation of silver nanoparticles (AgNPs) that allows these particles to have more efficient cytotoxic activity. In the current study, the extract of Marrubium alysson L., a plant of common occurrence in Egypt was used to synthesize AgNPs for the first time, where comparison of anticancer activity of crude and phenolic extracts with the AgNPs were extensively studied against cancer cell lines PC-3 and HCT-116. Interestingly, AgNPs of the crude extract exhibited promising cytotoxicity with IC50 values of 10.4 and 16.3 µg/ml, while AgNPs of the phenolic extract exhibited very potent cytotoxicity with IC50 values of 2.66 and 1.34 µg/ml compared to Doxorubicin (as a standard reference drug) that exhibited IC50 values of 5.13 and 4.36 µg/ml, respectively against the tested cells. Additionally, AgNPs of the phenolic extract induced apoptosis in HCT-116 with a higher ratio than in PC-3 cells. It induced apoptosis in PC-3 cells by 79.3-fold change, while it induced total colon apoptotic cell death by 228.3-fold change compared to untreated control. Finally, the apoptotic activity of AgNPs of the phenolic extract in the treated PC-3 and HCT-116 cells was confirmed using RT-PCR. As a result, AgNPs of the phenolic extract could be considered a promising anticancer candidate through apoptosis-induction.Communicated by Ramaswamy H. Sarma.

A New Saponin (Zygo-albuside D) from Zygophyllum album Roots Triggers Apoptosis in Non-Small Cell Lung Carcinoma (A549 Cells) through CDK-2 Inhibition.

Phytochemical study of the ethyl acetate root extract of Zygophyllum album has resulted in the isolation of a new saponin, Zygo-albuside D (1), along with two known compounds; (3-O-[ß-D-quinovopyranosyl]-quinovic acid) (2), which is first reported in the root, and catechin (3), first reported in the genus. Their chemical structures were established by NMR and high-resolution mass spectrometry (HRMS). The new saponin (1) exhibited promising cytotoxicity with IC50 values of 3.5 and 5.52 µM on A549 and PC-3 cancer cell lines, respectively, compared to doxorubicin with IC50 values of 9.44 and 11.39 µM on A549 and PC-3 cancer cell lines, respectively. While it had an IC50 value of 46.8 µM against WISH cells. Investigating apoptosis-induction, compound 1 induced total apoptotic cell death in A549 lung cancer cells by 32-fold; 21.53% compared to 0.67% in the untreated control cells. Finally, it upregulated the pro-apoptotic genes and downregulated the antiapoptotic gene using gene expression levels. Compound 1 exhibited remarkable CDK-2 target inhibition by 96.2% with an IC50 value of 117.6 nM compared to Roscovitine. The molecular docking study further confirmed the binding affinity of compound 1 as CDK2 and Bcl2 inhibitors that led to apoptosis induction in A549 cancer cells. Hence, this study highlights the importance of compound 1 in the design of a new anticancer agent with specific mechanisms.

Antimicrobial Potential of Different Isolates of Chaetomium globosum Combined with Liquid Chromatography Tandem Mass Spectrometry Chemical Profiling.

The antimicrobial resistance of pathogenic microorganisms against commercial drugs has become a major problem worldwide. This study is the first of its kind to be carried out in Egypt to produce antimicrobial pharmaceuticals from isolated native taxa of the fungal Chaetomium, followed by a chemical investigation of the existing bioactive metabolites. Here, of the 155 clinical specimens in total, 100 pathogenic microbial isolates were found to be multi-drug resistant (MDR) bacteria. The Chaetomium isolates were recovered from different soil samples, and wild host plants collected from Egypt showed strong inhibitory activity against MDR isolates. Chaetomium isolates displayed broad-spectrum antimicrobial activity against C. albicans, Gram-positive, and Gram-negative bacteria, with inhibition zones of 11.3 to 25.6 mm, 10.4 to 26.0 mm, and 10.5 to 26.5 mm, respectively. As a consecutive result, the minimum inhibitory concentration (MIC) values of Chaetomium isolates ranged from 3.9 to 62.5 µg/mL. Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) analysis was performed for selected Chaetomium isolates with the most promising antimicrobial potential against MDR bacteria. The LC-MS/MS analysis of Chaetomium species isolated from cultivated soil at Assuit Governate, Upper Egypt (3), and the host plant Zygophyllum album grown in Wadi El-Arbaein, Saint Katherine, South Sinai (5), revealed the presence of alkaloids as the predominant bioactive metabolites. Most detected bioactive metabolites previously displayed antimicrobial activity, confirming the antibacterial potential of selected isolates. Therefore, the Chaetomium isolates recovered from harsh habitats in Egypt are rich sources of antimicrobial metabolites, which will be a possible solution to the multi-drug resistant bacteria tragedy.