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1.
Sci Rep ; 13(1): 22486, 2023 12 15.
Article in English | MEDLINE | ID: mdl-38110432

ABSTRACT

A novel series of α-cyano indolylchalcones was prepared, and their chemical structures were confirmed based on the different spectral data. Among them, compound 7f was observed to be the most effective bioactive chalcone with distinguished potency and selectivity against colorectal carcinoma (HCT116) with IC50 value (6.76 µg/mL) relative to the positive control (5 FU) (77.15 µg/mL). In a preliminary action study, the acrylonitrile chalcone 7f was found to enhance apoptotic action via different mechanisms like inhibition of some anti-apoptotic protein expression, regulation of some apoptotic proteins, production of caspases, and cell cycle arrest. All mechanisms suggested that compound 7f could act as a professional chemotherapeutic agent. Also, a molecular docking study was achieved on some selected proteins implicated in cancer (Caspase 9, XIAP, P53 mutant Y220C, and MDM2) which showed variable interactions with compound 7f with good Gibbs free energy scores.


Subject(s)
Acrylonitrile , Antineoplastic Agents , Carcinoma , Chalcones , Colonic Neoplasms , Humans , Tumor Suppressor Protein p53/metabolism , Acrylonitrile/pharmacology , Molecular Docking Simulation , Chalcones/pharmacology , Chalcones/chemistry , HCT116 Cells , Apoptosis , Colonic Neoplasms/drug therapy , Indoles/pharmacology , Antineoplastic Agents/chemistry , Cell Proliferation
2.
Heliyon ; 9(6): e16656, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37332941

ABSTRACT

There are two major problems in the world, fuel deficiency and environmental pollution by fossil fuels. Microalgae are regarded as one of the most feasible feedstocks for the manufacturing of biofuels and are used in the degradation of fossil fuel spills. The present study was possessed to investigate the ability of green alga Chlorella vulgaris, blue-green alga Synechococcus sp, and its consortium to grow and degrade hydrocarbon such as kerosene (k) with different concentrations (0, 0.5, 1, and 1,5%), and also using algal biomasses to produce biofuel. The algal growth was estimated by optical density (O.D) at 600 nm, pigment contents such as Chlorophyll a,b carotenoid, and dry weight. The kerosene degradation was estimated by FT-IR analysis after and before the cultivation of algae and its consortium. The components of the methanol extract were determined by GC-MS spectroscopy. The results denote the best growth was determined by O.D, algae consortium with 1.5% Kerosene after ten days, meanwhile, the highest dry weight was with C. vulgaris after ten days of cultivation. The FT-IR demonstrated the algae and consortium possessed high efficacy to degrade kerosene. After 15 days of algae cultivation with 1% K, C.vulgaris produced the maximum amount of lipids (32%). The GC-MS profile of methanol extract of two algae and consortium demonstrated that Undecane was presented in high amounts, C.vulgaris (19.9%), Synechococcussp (82.16%), algae consortium (79.51%), and also were presented moderate amounts of fatty acid methyl ester in Synechococcus sp. Overall, our results indicate that a consortium of algae can absorb and remove kerosene from water, and at the same time produce biofuels like biodiesel and petroleum-based fuels.

3.
Naunyn Schmiedebergs Arch Pharmacol ; 396(4): 719-736, 2023 04.
Article in English | MEDLINE | ID: mdl-36469109

ABSTRACT

A new chalcone series has been developed that may be useful in the treatment of lung cancer. The new series was confirmed by the different spectral tools. MTT assay was used to detect the cytotoxic effect of the novel chalcones against lung cancer cell line (A549). Molecular docking studies were performed on the most two effective chalcones 7b and 7c. Different molecular techniques were utilized to study the activity and the effect of two chalcones 7b and 7c on apoptosis of A549 cell line.


Subject(s)
Antineoplastic Agents , Carcinoma , Chalcones , Lung Neoplasms , Humans , Chalcones/pharmacology , Chalcones/therapeutic use , Molecular Docking Simulation , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , A549 Cells , Lung/pathology , Furans/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Structure-Activity Relationship , Apoptosis , Cell Proliferation , Cell Line, Tumor
4.
Microorganisms ; 12(1)2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38276170

ABSTRACT

Dental caries is an infectious oral disease caused by the presence of different bacteria in biofilms. Multidrug resistance (MDR) is a major challenge of dental caries treatment. Swabs were taken from 65 patients with dental caries in Makkah, Saudi Arabia. Swabs were cultivated on mitis salivarius agar and de Man, Rogosa, and Sharpe (MRS) agar. VITEK 2 was used for the identification of isolated bacteria. Antibiotic susceptibility testing of the isolated bacteria was performed using commercial antibiotic disks. Ulva lactuca was used as a reducing agent and cellulose source to create nanocellulose and Ag/cellulose nanocomposites. Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction spectroscopy (XRD) were used to characterize nanocellulose and Ag/cellulose nanocomposites. The results showed that most bacterial isolates were Streptococcus spp., followed by Staphylococcus spp. on mitis salivarius media. Lactobacillus spp. and Corynebacterium group f-1 were the bacterial isolates on de Man, Rogosa, and Sharpe (MRS) media. The antibiotic susceptibility test revealed resistance rates of 77%, 93%, 0, 83%, 79%, and 79% against penicillin G, Augmentin, metronidazole, ampicillin, ciprofloxacin, and cotrimoxazole, respectively. Ag/cellulose nanocomposites and Ag/cellulose nanocomposites with fluoride were the most effective antibacterial agents. The aim of this work was to assess the antibacterial activity of Ag/cellulose nanocomposites with and without fluoride against bacteria isolated from the oral cavities of patients with dental caries. This study demonstrated that Ag/cellulose nanocomposites have antibacterial properties against multidrug-resistant bacteria that cause dental caries.

5.
Molecules ; 27(21)2022 Oct 29.
Article in English | MEDLINE | ID: mdl-36364191

ABSTRACT

This work aims to characterize the haloarchaeal diversity of unexplored environmental salty samples from a hypersaline environment on the southern coast of Jeddah, Saudi Arabia, looking for new isolates able to produce polyhydroxyalkanoates (PHAs). Thus, the list of PHA producers has been extended by describing two species of Halolamina; Halolamina sediminis sp. strain NRS_35 and unclassified Halolamina sp. strain NRS_38. The growth and PHA-production were investigated in the presence of different carbon sources, (glucose, sucrose, starch, carboxymethyl cellulose (CMC), and glycerol), pH values, (5-9), temperature ranges (4-65 °C), and NaCl concentrations (100-350 g L-1). Fourier-transform infra-red analysis (FT-IR) and Liquid chromatography-mass spectrometry (LC-MS) were used for qualitative identification of the biopolymer. The highest yield of PHB was 33.4% and 27.29% by NRS_35 and NRS_38, respectively, using starch as a carbon source at 37 °C, pH 7, and 25% NaCl (w/v). The FT-IR pattern indicated sharp peaks formed around 1628.98 and 1629.28 cm-1, which confirmed the presence of the carbonyl group (C=O) on amides and related to proteins, which is typical of PHB. LC-MS/MS analysis displayed peaks at retention times of 5.2, 7.3, and 8.1. This peak range indicates the occurrence of PHB and its synthetic products: Acetoacetyl-CoA and PHB synthase (PhaC). In summary, the two newly isolated Halolamina species showed a high capacity to produce PHB using different sources of carbon. Further research using other low-cost feedstocks is needed to improve both the quality and quantity of PHB production. With these results, the use of haloarchaea as cell factories to produce PHAs is reinforced, and light is shed on the global concern about replacing plastics with biodegradable polymers.


Subject(s)
Polyhydroxyalkanoates , Sodium Chloride , Sodium Chloride/metabolism , Spectroscopy, Fourier Transform Infrared , Chromatography, Liquid , Tandem Mass Spectrometry , Polyhydroxyalkanoates/chemistry , Carbon/metabolism , Starch , Hydroxybutyrates/chemistry
6.
Front Pharmacol ; 13: 936996, 2022.
Article in English | MEDLINE | ID: mdl-35847018

ABSTRACT

Cancer can develop due to abnormal cell proliferation in any body's cells, so there are over a hundred different types of cancer, each with its distinct behavior and response to treatment. Therefore, many studies have been conducted to slow cancer progression and find effective and safe therapies. Nutraceuticals have great attention for their anticancer potential. Therefore, the current study was conducted to investigate the anticancer effects of curcumin (Cur), thymoquinone (TQ), and 3, 3'-diindolylmethane (DIM) combinations on lung (A549) and liver (HepG2) cancer cell lines' progression. Results showed that triple (Cur + TQ + DIM) and double (Cur + TQ, Cur + DIM, and TQ + DIM) combinations of Cur, TQ, and DIM significantly increased apoptosis with elevation of caspase-3 protein levels. Also, these combinations exhibited significantly decreased cell proliferation, migration, colony formation activities, phosphatidylinositol 3-kinase (PI3K), and protein kinase B (AKT) protein levels with S phase reduction. Triple and double combinations of Cur, TQ, and DIM hindered tumor weight and angiogenesis of A549 and HepG2 implants in the chorioallantoic membrane model. Interestingly, Cur, TQ, and DIM combinations are considered promising for suppressing cancer progression via inhibiting tumor angiogenesis. Further preclinical and clinical investigations are warranted.

7.
Molecules ; 27(10)2022 May 13.
Article in English | MEDLINE | ID: mdl-35630600

ABSTRACT

Calotropis procera (C. procera) is a wild shrub that is a medicinal plant found in abundance throughout Saudi Arabia. In this study, we investigated the phytochemical composition and antigenotoxic properties of the ethanolic extract of C. procera, in addition to the antimicrobial activity of the plant and its rhizospheric actinobacteria effects against pathogenic microorganisms. Soil-extract medium supplemented with glycerol as a carbon source and starch-casein agar medium was used for isolation of actinobacteria from rhizosphere. From the plant, a total of 31 compounds were identified using gas chromatography/mass spectrometry (GC-MS). The main components were α-amyrin (39.36%), lupeol acetate (17.94%), phytol (13.32%), hexadecanoic acid (5.55%), stigmasterol (3.16%), linolenic acid (3.04%), and gombasterol A (2.14%). C. procera plant extract's antimicrobial activity was investigated using an agar well-diffusion assay and minimum inhibitory concentration (MIC) against six pathogenic microbial strains. The plant extract of C. procera was considered significantly active against Staphylococcus aureus, Klebsiella pneumonia, and Escherichia coli, with inhibition zones of 18.66 mm, 21.26 mm, and 21.93 mm, respectively. The plant extract was considered to be a moderate inhibitor against Bacillus subtilis, with MIC ranging from 0.60-1.50 mg/mL. On the other hand, the isolated actinobacteria were considered to be a moderate inhibitor against S. aureus (MIC of 86 µg/mL), and a potent inhibitor, strain CALT_2, against Candida albicans (MIC of 35 µg/mL). The 16S rRNA gene sequence analysis showed that the potential strains belonged to the genus Streptomyces. The effect of C. procera extract against cyclophosphamide (CP)-induced genotoxicity was examined by evaluating chromosome abnormalities in mouse somatic cells and DNA fragmentation assays. The current study revealed that oral pretreatment of C. procera (50, 100, and 200 mg/kg b.w.) for 1, 7, and 14 days to cyclophosphamide-treated animals significantly reduced chromosomal abnormalities as well as DNA fragmentation in a dose-dependent manner. Moreover, C. procera extract had antimicrobial and antigenotoxic effects against CP-induced genotoxicity.


Subject(s)
Actinobacteria , Anti-Infective Agents , Calotropis , Streptomyces , Actinobacteria/genetics , Agar , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/chemistry , Calotropis/chemistry , Cyclophosphamide , Mice , Plant Extracts/chemistry , RNA, Ribosomal, 16S , Rhizosphere , Staphylococcus aureus , Streptomyces/genetics
8.
Integr Cancer Ther ; 21: 15347354221099537, 2022.
Article in English | MEDLINE | ID: mdl-35583244

ABSTRACT

Breast cancer is the most harmful malignancy in women worldwide. Therefore, in the current study, we investigated the combinatory effect of natural bioactive compounds, including curcumin (Cur) and thymoquinone (TQ), on MCF7 and MDA-MB-231 breast cancer cell lines' progression. We investigated the Fa values and combination index of Cur and TQ in this context. Moreover, cytotoxicity percentages, annexin-V, proliferation, colony formation, and migration assays were used along with cell cycle analysis. In addition, caspase-3, phosphatidylinositol 3-kinase (PI3K), and protein kinase B (AKT) protein levels were determined by ELISA assessment. The results showed that Cur, TQ, and Cur + TQ induced apoptosis with cell cycle arrest and decreased cell proliferation, colony formation, and migration activities. Cur + TQ combination significantly increased caspase-3 and decreased PI3K and AKT protein levels. These results suggest the promising anticancer benefit of the Cur and TQ combination against breast cancer.


Subject(s)
Breast Neoplasms , Curcumin , Apoptosis , Benzoquinones/pharmacology , Breast Neoplasms/metabolism , Caspase 3 , Cell Line, Tumor , Cell Proliferation , Curcumin/pharmacology , Female , Humans , MCF-7 Cells , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt
9.
Integr Cancer Ther ; 20: 15347354211035450, 2021.
Article in English | MEDLINE | ID: mdl-34490824

ABSTRACT

Doxorubicin (Dox) induces senescence in numerous cancer cell types, but these senescent cancer cells relapse again if they are not eliminated. On this principle, we investigated the apoptotic effect of thymoquinone (TQ), the active ingredient of Nigella sativa seeds and costunolide (COS), the active ingredient of Costus speciosus, on the senescent colon (Sen-HCT116) and senescent breast (Sen-MCF7) cancer cell lines in reference to their corresponding proliferative cells to rapidly eliminate the senescent cancer cells. The senescence markers of Sen-HCT116 and Sen-MCF7 were determined by a significant decrease in bromodeoxyuridine (BrdU) incorporation and significant increases in SA-ß-gal, p53, and p21 levels. Then proliferative, Sen-HCT116, and Sen-MCF7 cells were subjected to either TQ (50 µM) or COS (30 µM), the Bcl2-associated X protein (Bax), B-cell lymphoma 2 (Bcl2), caspase 3 mRNA expression and its activity were established. Results revealed that TQ significantly increased the Bax/Bcl2 ratio in HCT116 + Dox5 + TQ, MCF7 + TQ, and MCF7 + Dox5 + TQ compared with their corresponding controls. COS significantly increased the Bax/Bcl2 ratio in HCT116 + Dox5 + TQ and MCF7 + Dox5 + TQ compared with their related controls. Also, TQ and COS were significantly increased caspase 3 activity and cell proliferation of Sen-HCT116 and Sen-MCF7. The data revealed a higher sensitivity of senescent cells to TQ or COS than their corresponding proliferative cells.


Subject(s)
Apoptosis , Neoplasm Recurrence, Local , Benzoquinones , Colon , Doxorubicin/pharmacology , Humans , Sesquiterpenes
10.
Sci Rep ; 11(1): 16468, 2021 08 13.
Article in English | MEDLINE | ID: mdl-34389757

ABSTRACT

Paecilomyces variotii xylanase was, produced in stirred tank bioreactor with yield of 760 U/mL and purified using 70% ammonium sulfate precipitation and ultra-filtration causing 3.29-fold purification with 34.47% activity recovery. The enzyme purity was analyzed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) confirming its monomeric nature as single band at 32 KDa. Zymography showed xylan hydrolysis activity at the same band. The purified enzyme had optimum activity at 60 °C and pH 5.0. The pH stability range was 5-9 and the temperature stability was up 70 °C. Fe2+and Fe3+ exhibited inhibition of xylanase enzyme while Cu2+, Ca2+, Mg2+ and Mn2+ stimulated its activity. Mercaptoethanol stimulated its activity; however, Na2-EDTA and SDS inhibited its activity. The purified xylanase could hydrolyze beechwood xylan but not carboxymethyl cellulose (CMC), avicel or soluble starch. Paecilomyces variotii xylanase Km and Vmax for beechwood were determined to be 3.33 mg/mL and 5555 U/mg, respectively. The produced xylanase enzyme applied on beech xylan resulted in different types of XOS. The antioxidant activity of xylo-oligosaccharides increased from 15.22 to 70.57% when the extract concentration was increased from 0.1 to 1.5 mg/mL. The enzyme characteristics and kinetic parameters indicated its high efficiency in the hydrolysis of xylan and its potential effectiveness in lignocellulosic hydrolysis and other industrial application. It also suggests the potential of xylanase enzyme for production of XOS from biomass which are useful in food and pharmaceutical industries.


Subject(s)
Antioxidants/metabolism , Byssochlamys/metabolism , Endo-1,4-beta Xylanases/metabolism , Glucuronates/metabolism , Oligosaccharides/metabolism , Bioreactors , Byssochlamys/enzymology , Electrophoresis, Polyacrylamide Gel , Endo-1,4-beta Xylanases/isolation & purification , Hydrogen-Ion Concentration
11.
Biomedicines ; 9(8)2021 Aug 10.
Article in English | MEDLINE | ID: mdl-34440193

ABSTRACT

Costunolide (COS) is a sesquiterpene lactone with anticancer properties. The present study investigated the anticancer effects of COS against the human colon (HCT116) and breast (MDA-MB-231-Luc) cancer cell lines. Inhibition of cell lines viability and IC50 of COS were assessed via an MTT assay. Furthermore, the apoptotic rate was detected by assessment of Bcl2-associated X (Bax) and B-cell lymphoma 2 (Bcl2) protein levels by flow cytometry. Xenograft mice model of HCT116 and MDA-MB-231-Luc were carried out to determine the effect of COS and its nanoparticles (COS-NPs). The results demonstrated that COS inhibited the viability of HCT116 and MDA-MB-231-Luc cells, with a half maximal inhibitory concentration value (IC50) of 39.92 µM and 100.57 µM, respectively. COS significantly increased Bax and decreased Bcl2 levels in treated cells. COS and COS-NPs, in combination with doxorubicin (DOX), significantly decreased the tumor growth of HCT116 and MDA-MB-231-Luc implants in mice. Furthermore, oral administration of COS and COS-NPs significantly decreased the viable cells and increased necrotic/apoptotic cells of HCT116 and MDA-MB-231-Luc implants. Interestingly, both COS and COS-NPs protected the cardiac muscles against DOX's cardiotoxicity. The current results indicated the promising anticancer and cardiac muscles protection of COS and COS-NPs when administered with chemotherapy.

12.
Bioorg Chem ; 114: 105147, 2021 09.
Article in English | MEDLINE | ID: mdl-34246114

ABSTRACT

An efficient route for the preparation of new heterocyclic cyanoacrylamides based p-fluorophenyl and p-phenolic compounds was depicted. All structures were confirmed based on the different spectral tools and elemental analyses. MTT assay for the novel synthesized series was performed against four different cell lines (A549, MCF7, Hepg2, and Wi38). Among all tested groups, the p-phenolic compound 10 (207.1 µg/ml) and the corresponding p-fluorophenyl derivative 6 (325.7 µg/ml) were selected for further simulation and molecular studies against liver carcinoma. Compounds 6 and 10 were investigated theoretically to different protein sets as (cdk2, Bcl2-xl, cIAP1-BIR3, and MDM2) and they illustrated different binding affinities. The computational studies and different molecular techniques (e.g. cell cycle analysis, DPA assay, relative gene expression, and ELISA assay) were utilized in this report.


Subject(s)
Acrylamide/pharmacology , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Carcinoma, Hepatocellular/drug therapy , Heterocyclic Compounds/pharmacology , Liver Neoplasms/drug therapy , Phenols/pharmacology , Acrylamide/chemistry , Antineoplastic Agents/chemistry , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Heterocyclic Compounds/chemistry , Humans , Liver Neoplasms/pathology , Molecular Docking Simulation , Molecular Structure , Phenols/chemistry , Structure-Activity Relationship
13.
AMB Express ; 11(1): 75, 2021 May 26.
Article in English | MEDLINE | ID: mdl-34041605

ABSTRACT

Haloferax sp strain NRS1 (MT967913) was isolated from a solar saltern on the southern coast of the Red Sea, Jeddah, Saudi Arabia. The present study was designed for estimate the potential capacity of the Haloferax sp strain NRS1 to synthesize (silver nanoparticles) AgNPs. Biological activities such as thrombolysis and cytotoxicity of biosynthesized AgNPs were evaluated. The characterization of silver nanoparticles biosynthesized by Haloferax sp (Hfx-AgNPs) was analyzed using UV-vis spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). The dark brown color of the Hfx-AgNPs colloidal showed maximum absorbance at 458 nm. TEM image analysis revealed that the shape of the Hfx-AgNPs was spherical and a size range was 5.77- 73.14 nm. The XRD spectra showed a crystallographic plane of silver nanoparticles, with a crystalline size of 29.28 nm. The prominent FTIR peaks obtained at 3281, 1644 and 1250 cm- 1 identified the Functional groups involved in the reduction of silver ion reduction to AgNPs. Zeta potential results revealed a negative surface charge and stability of Hfx-AgNPs. Colloidal solution of Hfx-AgNPs with concentrations ranging from 3.125 to 100 µg/mL was used to determine its hemolytic activity. Less than 12.5 µg/mL of tested agent showed no hemolysis with high significant decrease compared with positive control, which confirms that Hfx-AgNPs are considered non-hemolytic (non-toxic) agents according to the ISO/TR 7405-1984(f) protocol. Thrombolysis activity of Hfx-AgNPs was observed in a concentration-dependent manner. Further, Hfx-AgNPs may be considered a promising lead compound for the pharmacological industry.

14.
Sci Rep ; 11(1): 3555, 2021 02 11.
Article in English | MEDLINE | ID: mdl-33574404

ABSTRACT

Textile wastewater contains large quantities of azo dyes mixed with various contaminants especially heavy metal ions. The discharge of effluents containing methyl orange (MO) dye and Cu2+ ions into water is harmful because they have severe toxic effects to humans and the aquatic ecosystem. The dried algal biomass was used as a sustainable, cost-effective and eco-friendly for the treatment of the textile wastewater. Box-Behnken design (BBD) was used to identify the most significant factors for achieving maximum biosorption of Cu2+ and MO from aqueous solutions using marine alga Fucus vesiculosus biomass. The experimental results indicated that 3 g/L of F. vesiculosus biomass was capable of removing 92.76% of copper and 50.27% of MO simultaneously from aqueous solution using MO (60 mg/L), copper (200 mg/L) at pH 7 within 60 min with agitation at 200 rpm. The dry biomass was also investigated using SEM, EDS, and FTIR before and after MO and copper biosorption. FTIR, EDS and SEM analyses revealed obvious changes in the characteristics of the algal biomass as a result of the biosorption process. The dry biomass of F. vesiculosus can eliminate MO and copper ions from aquatic effluents in a feasible and efficient method.


Subject(s)
Biodegradation, Environmental , Fucus/chemistry , Phaeophyceae/chemistry , Anions/chemistry , Anions/toxicity , Azo Compounds/chemistry , Azo Compounds/toxicity , Cations/chemistry , Cations/toxicity , Copper/chemistry , Copper/toxicity , Fucus/metabolism , Ions/chemistry , Ions/toxicity , Phaeophyceae/metabolism
15.
Bioorg Chem ; 103: 104195, 2020 10.
Article in English | MEDLINE | ID: mdl-32896741

ABSTRACT

A novel set of 2-cyanoacrylamides linked to ethyl 1,3-diphenylpyrazole-4-carboxylates moiety were synthesized and elucidated by different spectroscopic tools. In vitro cytotoxic assay was carried out against different cell lines (Hct116, A549, MDA-MB231, and HFB4). Ethyl 5-(2-cyano-3-(furan-2-yl)acrylamido)-1,3-diphenylpyrazole-4-carboxylate 5 achieved the potent cytotoxic effect toward all tested cancer cell lines especially colon cancer (HCT116) with IC50 value (30.6 µg/ml) relative to the lead compound 3 and the standard positive control 5-FU. Additionally, it exhibited less toxic effect toward the normal human melanocytes (HFB4) cell line. Compound 5 was theoretically investigated and compared for its binding affinity to a model of protein markers relative to the lead compound 3 using two different molecular docking programs. More investigations were performed in an attempt to find out the molecular mechanism of this novel compound inside colon cancer cells, as real time PCR analysis, Elisa assay, flow cytometry, and morphological characterizations using TEM and SEM tools.Herein, we showed that compound 5 interferes with the intrinsic pathway of apoptosis at the mitochondrial level in response to an apoptogenic stimulus as cytochromec, caspase-9 and caspases-3 which were triggered by our novel compound 5. All molecular investigations proved that intrinsic apoptotic pathway of colorectal carcinoma was strongly initiated by the effect of compound 5 through upregulation of mitochondrial apoptosis related genes as (Caspase-3, caspase-9, BAX, P53, and cytochrome-c) and down-regulated anti-apoptotic proteins (BCL2, MMP1, CDK4, and VEGFR). Further studies proved cell cycle arrest of HCT116 cell lines at G2/M phase after treatment. In addition, our data revealed that our novel efficiently damage the genomic DNA of colorectal cells involving P53 dependent mechanism using DPA assay. Sever morphological and ultrastructural changes were detected in colorectal cells treated by compound 5 compared to control using both scanning electron microscopy (SEM) and transmission electron microscopy (TEM).


Subject(s)
Acrylamides/pharmacology , Antineoplastic Agents/pharmacology , Colorectal Neoplasms/drug therapy , Mitochondria/drug effects , Nitriles/pharmacology , Pyrazoles/pharmacology , Acrylamides/chemical synthesis , Acrylamides/metabolism , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/metabolism , Apoptosis/drug effects , Binding Sites , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Molecular Docking Simulation , Nitriles/chemical synthesis , Nitriles/metabolism , Protein Binding , Pyrazoles/chemical synthesis , Pyrazoles/metabolism , bcl-X Protein/chemistry , bcl-X Protein/metabolism
16.
Sci Rep ; 10(1): 15923, 2020 Sep 23.
Article in English | MEDLINE | ID: mdl-32963274

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

17.
Sci Rep ; 10(1): 13479, 2020 08 10.
Article in English | MEDLINE | ID: mdl-32778759

ABSTRACT

A large number of industries use heavy metal cations to fix dyes in fabrication processes. Malachite green (MG) is used in many factories and in aquaculture production to treat parasites, and it has genotoxic and carcinogenic effects. Chromium is used to fix the dyes and it is a global toxic heavy metal. Face centered central composite design (FCCCD) has been used to determine the most significant factors for enhanced simultaneous removal of MG and chromium ions from aqueous solutions using marine green alga Enteromorpha intestinalis biomass collected from Jeddah beach. The dry biomass of E. intestinalis samples were also examined using SEM and FTIR before and after MG and chromium biosoptions. The predicted results indicated that 4.3 g/L E. intestinalis biomass was simultaneously removed 99.63% of MG and 93.38% of chromium from aqueous solution using a MG concentration of 7.97 mg/L, the chromium concentration of 192.45 mg/L, pH 9.92, the contact time was 38.5 min with an agitation of 200 rpm. FTIR and SEM proved the change in characteristics of algal biomass after treatments. The dry biomass of E. intestinalis has the capacity to remove MG and chromium from aquatic effluents in a feasible and efficient manner.


Subject(s)
Chromium/toxicity , Rosaniline Dyes/toxicity , Ulva/metabolism , Water Purification/economics , Adsorption , Biodegradation, Environmental , Biomass , Cost-Benefit Analysis , Hydrogen-Ion Concentration , Ions , Kinetics , Metals, Heavy , Temperature , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/economics , Water Purification/methods
18.
Int J Nanomedicine ; 15: 2259-2268, 2020.
Article in English | MEDLINE | ID: mdl-32280218

ABSTRACT

PURPOSE: This study was designed to determine the potential effect of nanoencapsulated bioactive compounds from different natural sources on human pancreatic cancer. BACKGROUND: Pancreatic cancer carries the highest fatality rate among all human cancers because of its high metastatic potential and late presentation at the time of diagnosis. Hence there is a need for improved methods to prevent and treat it. Natural products, such as 3, 3'-diindolylmethane (DIM) and ellagic acid (EA) demonstrated anticancer efficacy against various cancer types. However, DIM is insoluble. Hence, using nanotechnology to encapsulate these compounds in combination with EA might improve their physical and chemical properties and their delivery to the cancer cells. METHODS: Human pancreatic cancer cells, namely SUIT2-luciferase transfected, were used to examine the effects of DIM or EA and their nanoformulation in poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) [PLGA-PEG] nanoparticles (NPs) on SUIT2-luciferase cell viability/proliferation over 24 hrs. Additionally, effects on tumor weight and angiogenesis were determined using the chick chorioallantoic membrane (CAM) tumor implant model. RESULTS: Both DIM and EA PLGA-PEG NPs resulted in rapid suppression of pancreatic cancer cell viability/proliferation within 24 hrs (P < 0.01), while the non-encapsulated DIM and EA did not show any significant effect on SUIT2 cancer cell viability or cell proliferation (MTT assay). In the CAM pancreatic cancer cell (SUIT2) implant model, results showed a greater suppression of tumor weight (P < 0.01), tumor cell viability, and tumor angiogenesis (P < 0.01) for DIM NPs and EA NPs and their combinations versus DIM or EA alone. CONCLUSION: Nanoformulation of DIM and EA resulted in a more effective suppression of pancreatic cancer cell viability, pancreatic tumor weight, implanted cancer cell viability, and tumor angiogenesis as compared with these bioactive compounds alone.


Subject(s)
Antineoplastic Agents/pharmacology , Biological Products/chemistry , Ellagic Acid/pharmacology , Indoles/pharmacology , Nanoparticles/chemistry , Pancreatic Neoplasms/drug therapy , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Biological Products/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Chick Embryo , Chorioallantoic Membrane/drug effects , Ellagic Acid/administration & dosage , Humans , Indoles/administration & dosage , Nanoparticles/therapeutic use , Pancreatic Neoplasms/pathology , Polyesters/chemistry , Polyethylene Glycols/chemistry
19.
Dose Response ; 17(2): 1559325819850425, 2019.
Article in English | MEDLINE | ID: mdl-31191184

ABSTRACT

Many plant-derived compounds have been used to treat microbial infections. Staphylococcus aureus a common cause of many organ infections, has generated increasing concern due to its resistance to antibacterial drugs. This work was carried out to explore the susceptibility of 6 strains (LN872136, LN872137, LN871238, LN871239, LN872140, and LN871241) of methicillin-resistant Staphylococcus aureus to aqueous extract of Lepidium sativum seeds in vitro. Various concentrations (5-20 mg/mL) were used to evaluate the effect of the extract on bacteria growth via the assessment of the microbial biomass and the inhibition zone (IZ). The results showed that the plant extract at 15 or 20 mg/mL, significantly decreased the the biomass of S aureus strains after 24 or 48 hours exposure period. Staphylococcus aureus (LN871241) showed the largest IZ at 20 mg/mL and documented by scanning electron microscope. The current work may suggest that L sativum seed extract can be candidate as a promising antimicrobial agent to treat infection with methicillin-resistant S aureus.

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