This study focused on developing new inhibitors for the MCF-7 cell line to contribute to our understanding of breast cancer biology and various experimental techniques. 3D QSAR modeling was used to ...design new tetrahydrobenzo4, 5thieno2, 3-dpyrimidine derivatives with good characteristics. Two robust 3D-QSAR models were developed, and their predictive capacities were confirmed through high correlations CoMFA (Q 2 = 0.62, R 2 = 0.90) and CoMSIA (Q 2 = 0.71, R 2 = 0.88) via external validations (R 2 ext = 0.90 and R 2 ext = 0.91, respectively). These successful evaluations confirm the potential of the models to provide reliable predictions. Six candidate inhibitors were discovered, and two new inhibitors were developed in silico using computational methods. The ADME-Tox properties and pharmacokinetic characteristics of the new derivatives were evaluated carefully. The interactions between the new tetrahydrobenzo4, 5thieno2, 3-dpyrimidine derivatives and the protein ERα (PDB code: 4XO6) were highlighted by molecular docking. Additionally, MM/GBSA calculations and molecular dynamics simulations provided interesting information on the binding stabilities between the complexes. The pharmaceutical characteristics, interactions with protein, and stabilities of the inhibitors were examined using various methods, including molecular docking and molecular dynamics simulations over 100 ns, binding free energy calculations, and ADME-Tox predictions, and compared with the FDA-approved drug capivasertib. The findings indicate that the inhibitors exhibit significant binding affinities, robust stabilities, and desirable pharmaceutical characteristics. These newly developed compounds, which act as inhibitors to mitigate breast cancer, therefore possess considerable potential as prospective drug candidates.
Curcumin (CUR) and piperine (PP) are bioactive compounds with prominent pharmacological activities that have been investigated for the treatment of various diseases. The aim of the present study is ...to develop Bio-SNEDDS for CUR and PP as a combined delivery system for cancer therapy.
CUR and PP loaded Bio-SNEDDSs with varying compositions of bioactive lipid oils, surfactants, and cosolvents were prepared at room temperature. Bio-SNEDDSs were characterized using a Zetasizer Nano particle size analyzer and further examined by transmission electron microscopy (TEM) for morphology. The in vivo toxicity of the preparations of Bio-SNEDDS was investigated in wild-type zebrafish embryos and cytotoxicity in THP-1 (human leukemia monocytic cells), Jurkat (human T lymphocyte cells) and HUVEC (non-cancerous normal) cells.
Bio-SNEDDSs were successfully developed with black seed oil, Imwitor 988, Transcutol P and Cremophor RH40 at a ratio of 20/20/10/50 (%w/w). The droplet size, polydispersity index and zeta potential of the optimized Bio-SNEDDS were found to be 42.13 nm, 0.59, and -19.30 mV, respectively. Bio-SNEDDS showed a spherical structure evident by TEM analysis. The results showed that Bio-SNEDDS did not induce toxicity in zebrafish embryos at concentrations between 0.40 and 30.00 μg/mL. In TG (fli1: EGFP) embryos treated with Bio-SNEDDS, there was no change in the blood vessel structure. The O-dianisidine staining of Bio-SNEDDS treated embryos at 48 h post-fertilization also showed a significant reduction in the number of blood cells compared to mock (DMSO 0.1% V/V) treated embryos. Bio-SNEDDS induced significant levels of cytotoxicity in the hematological cell lines THP-1 and Jurkat, while low toxicity in normal HUVEC cell lines was observed with IC50 values of 18.63±0.23 μg/mL, 26.03 ± 1.5 μg/mL and 17.52 ± 0.22 μg/mL, respectively.
Bio-SNEDDS exhibited enhanced anticancer activity and could thus be an important new pharmaceutical formulation to treat leukemia.
The nutrient contents of
L. (white radish) leaves (RSLs) and roots are known to have promising vital effects. We comparatively investigated the leaves and roots of
grown in Saudi Arabia to estimate ...the total phenol and flavonoid contents using the standard colorimetric methods. The antioxidant activity of RSLs and
roots (RSRs) were measured by 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays. Both extracts’ cytotoxic activity was assessed by MTT assay against several human cancer cell lines (A549, HepG2, MDA-MB-231, and MCF-7). High-performance thin-layer chromatography was used to identify and quantify the biomarker compound rutin in both extracts. The total phenolic content in RSLs (125.3 mg of gallic acid equivalent GAE/g) was higher than that in roots (95.8 of GAE/g), whereas the flavonoid content (44.5 mg of quercetin equivalent QE/g) was almost double compared in RSR extract (24.4 of QE/g). Similarly, RSLs exhibited a higher antioxidative activity than RSRs in both DPPH (IC
216.8 vs 359.7 µg/mL) and ABTS (IC
326.7 vs 549 µg/mL) models. RSLs also demonstrated the highest antiproliferative efficiency against all cell lines, with IC
values of 217–453 µg/mL. The reversed-phase-high-performance thin-layer chromatography results showed the presence of rutin (5.2 µg/mg) only in RSLs. Our study indicates RSLs as a promising source of bioactive compounds compared with roots.
The essential oil of
(Konig ex Roxb.) Benth. (Synonym:
, Lamiaceae) collected from Saudi Arabia was studied utilizing GC and GC/MS. Forty four constituents were identified, representing 96.8% of the ...total oil. The
essential oil (MDEO) was characterized by a high content of oxygenated monoterpenes (76.2%). Camphor (54.3%) was the major compound in MDEO followed by 1,8-cineole (12.2%) and camphene (10.4%). Moreover, MDEO was assessed for its cytotoxic, antimicrobial, and antioxidant activities. MDEO demonstrated an interesting cytotoxic activity against all cancer cell lines with IC
values of 83.6 to 91.2 μg/mL, especially against MCF-7 cancer cells. Using labeling with annexin VFITC and/or propidium iodide (PI) dyes and flow cytometer analysis, the apoptosis induction was quantitatively confirmed for MCF-7 cells. The MDEO exhibited a considerable antimicrobial activity against all bacterial and fungal strains with minimum inhibitory concentration (MIC)-values of 0.07 to 1.25 mg/mL. The most sensitive microbial strain was
(MIC: 0.07 mg/mL). Minimum bactericidal concentration (MBC) or minimum fungicidal concentration (MFC) values were determined one time higher than that of MIC's. Additionally, the MDEO revealed a strong activity for reducing β-carotene bleaching with a total antioxidant value of 72.6% and significant DPPH free radical scavenging activity (78.4%) at the concentration 1000 μg/mL.
plants have a significant place in traditional medicine due to their numerous therapeutic properties, including their anti-tumor effects, which have been observed in several species. In the current ...study, a phytochemical investigation of
methanolic extract led to the isolation and characterization of four secondary metabolites from the chloroform (CHCl
) and ethyl acetate (EtOAc) fractions, which are reported for the first time in this species. One of the constituents, saudiarabicain F (
), is a rare C-19 oxidized ingol-type diterpenoid that has not been previously reported. The structures of these compounds were determined by extensive spectroscopic (HR-ESI-MS, 1D and 2D NMR) analyses. The anticancer properties of the
crude extract, its fractions and its isolated compounds were examined against several cancer cells. The active fractions were evaluated for their effects on cell-cycle progression and apoptosis induction using flow cytometry. Furthermore, RT-PCR was employed to estimate the gene-expression levels of the apoptosis-related genes. It was demonstrated that the
CHCl
and EtOAc fractions suppressed the proliferation of the cancer cells. The MCF-7 cells were the most sensitive to both fractions, with IC
values of 22.6 and 23.2 µg/mL, respectively. Notably, both fractions caused cell-cycle arrest in the G2/M phase of the treated MCF-7 cells. The inhibition of the MCF-7 cells' proliferation was also linked with apoptosis induction by flow-cytometry analysis. Additionally, the activation of apoptosis by both fractions was demonstrated by an increase in the ratio of Bax to Bcl-2, with an increase in the expression of caspase-7. Among the isolated compounds, glutinol (
) showed potent activity against the MCF-7 cell line, with an IC
value of 9.83 µg/mL. Our findings suggest that
has apoptosis-inducing effects and shows promise as a potential source of new chemotherapeutic drugs.
Pulicaria arabica has been traditionally utilized in folk medicine for various purposes such as ulcer treatments as well as antidiarrheal agent. Herein, the chemical profiles of Pulicaria arabica ...essential oils (PAEOs) and the in vitro antiproliferative effect of PAEOs were investigated. Hydrodistillation was employed to prepare PAEOs which were then characterized by GC/MS, while the antiproliferative effects were investigated by MTT assay as well as flow cytometric and RT-PCR analysis. Sixty-four (99.99 %) constituents were recognized from PAEOs. Carvotanacetone (36.97 %), (-)-carvomenthone (27.20 %) and benzene, 2-(1,1-dimethylethyl)-1,4-dimethoxy- (6.92 %) were the main components. PAEOs displayed IC50 values ranging from 30 to 50 μg/mL. DNA content analysis revealed that A549 cells exposed to PAEOs exhibited an increase in G1 cells population. The flow cytometry analysis results also showed that the PAEOs antiproliferative effect was mediated via apoptosis induction. Furthermore, a modulation in the pro-apoptotic markers (caspase-3 and Bax) and anti-apoptotic (Bcl-2) was also observed. In conclusion, PAEOs exhibited a moderate anti-proliferative effect on A549 cells through modulating the cell cycle progression and apoptosis initiation. These findings could offer a potential therapeutic use of PAEOs in lung cancer treatment.
The increase in antibiotic residues poses a serious threat to ecological and aquatic environments, necessitating the development of cost-effective, convenient, and recyclable adsorbents. In our ...study, we used cellulose-based layered double hydroxide (LDH) as an efficient adsorbent and nanocarrier for both sulfamethoxazole (SMX) and cefixime (CFX) residues due to their biodegradability and biocompatibility. Chemical processes are measured according to green chemistry metrics to identify which features adhere to the principles. A GREEnness Assessment (ESA), Analytical GREEnness Preparation (AGREEprep), and Analytical Eco-Scale Assessments (ESA) were used to assess the suitability of the proposed analytical method. We extensively analyzed the synthesized CoFe LDH/cellulose before and after the adsorption processes using XRD, FTIR, and SEM. We investigated the factors affecting the adsorption process, such as pH, adsorbent dose, concentrations of SMX and CFX and time. We studied six nonlinear adsorption isotherm models at pH 5 using CoFe LDH, which showed maximum adsorption capacities (qmax) of 272.13 mg/g for SMX and 208.00 mg/g for CFX. Kinetic studies were also conducted. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was performed on Vero cells in direct contact with LDH nanocomposites to evaluate the cytotoxicity and side effects of cellulose-based CoFe LDH. The cellulose-based CoFe LDH nanocomposite demonstrated excellent cytocompatibility and less cytotoxic effects on the tested cell line. These results validate the potential use of these unique LDH-based cellulose cytocompatible biomaterials for water treatment applications. The cost of the prepared adsorbents was investigated.
•Cellulose-based layered double hydroxide (LDH) as an adsorbent•Removal of drug residues.•A GREEnness Assessment (ESA), Analytical GREEnness Preparation (AGREEprep), and Analytical Eco-Scale Assessments (ESA).•Evaluation of the cytotoxicity.•Cost analysis.
In this study, in vitro and in vivo methods were used to evaluate the cytotoxicity and genotoxicity properties of silver nanoparticles (Ag-NPs) made from a crude ethanolic extract of Salacia ...chinensis. The test Ag-NPs had no cytotoxicity on the fibroblast cell line at a concentration of 100 μg/mL, according to the MTT assay results. The Chinese hamster ovary (CHO) cell line treated with varied concentrations of test Ag-NPs, with a maximum concentration of 200 μg/mL, did not exhibit any appreciable genotoxic activity, either by comparing the results with positive controls of genotoxicity caused by Methyl methane sulfonate and Benzo (a) pyrene at the concentration of 20 μg/mL, the lack of genotoxicity was established. An in vivo study in Swiss albino mice using various concentrations (250, 500, and 1000 mg/kg) of test Ag-NPs, which were compared with positive controls, further confirmed this in vitro result pattern. Contrary to the genotoxicity caused by the positive control, mouse bone marrow micronucleus testing findings revealed the absence of genotoxicity. These findings imply that at the measured doses, the Ag-NPs produced from the crude ethanolic extract of Salacia chinensis do not exhibit any cytotoxicity or genotoxicity.
•The AgNPs not causing cytotoxicity on fibroblast cellline at100 μg/mL concentration.•No chromosomal aberration found in CHO cellline at 200 μg mL−1 dosage of AgNPs.•The AgNPs not inducing any genotoxicity on both in-vitro and in-vivo studies.•The animal study proved that absence of genotoxicity on bone marrow micronucleus test.•S. chinensis synthesized AgNPs not causing cytotoxicity and genotoxicity.
and
are two Moroccan endemic medicinal plants used traditionally by the local population. The present study aims to investigate their essential oil chemical composition, antioxidant and antibacterial ...activities. The chemical composition of the essential oils was determined using the GC-MS analysis, the antioxidant activity assessed using DPPH and FRAP methods while the antimicrobial activity was evaluated against nine bacteria species tested (
,
,
,
, sensitive
, sensitive
, resistant
, resistant
and
). The major identified compounds of
essential oil where carvacrol (75%) and
-cymene (10.58%) while carvacrol (60.79%), thymol (12.9%),
-cymene (6.21%) and
-terpinene (4.47%) are the main compounds in
essential oil. The bioactivity of the essential oils of the two species of thyme was explained by their richness in oxygenated monoterpenes known for their great effectiveness with an IC
of 3.48 ± 0.05 and 4.88 ± 0.04 μL/mL and EC
of 0.12 ± 0.01 and 0.20 ± 0.02 μL/mL in the DPPH and FRAP assays, respectively, with an important antibacterial activity. These results encourage the use of these plants as a source of natural antioxidants, and antibacterial additives, to protect food from oxidative damage and to eliminate bacteria that are responsible for nosocomial infections.
Current treatments for complex diseases have remarkable side effects that negatively impact patients’ quality of life. Thus, natural compounds with fewer side effects represent a promising source for ...safe drugs. The genus Senecio is widely used in folk medicine due to its various pharmacological properties. In the present study, the total phenolic content of Senecio glaucus, which is grown in Saudi Arabia, was assessed using the Folin-Ciocalteau colorimetric method. Scavenging DPPH and ABTS assays were utilized to determine the antioxidant properties of S. glaucus fractions, and MTT assay was used to screen the cytotoxic activity of S. glaucus against various cancer cells. In addition, HPLC-UV was utilized to detect the presence of two phenolic acids, namely, vanillic acid (VA) and gallic acid (GA). Among all fractions tested, S. glaucus chloroform fraction (SGCF) yielded the highest value (125.3 mg·GA/g) in terms of total phenolic content. SGCF also exhibited the highest scavenging activities (76.7 and 74.1%) on both DPPH and ABTS assays, respectively. Similarly, SGCF also possessed the most potent cytotoxic activity against the MCF-7 cell line, with an IC50 value of 41.8 μg/ml. The validated HPLC method confirmed the presence of VA (4.8 μg/mg DW) and GA (3.9 μg/mg DW) in SGCF. Overall, our data show that S. glaucus had antioxidant and cytotoxic properties. A developed validated HPLC method which could be helpful for quantifying phenolic compounds in S. glaucus was established.
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