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In the present work, the extensive biological activities of marine endophytic Streptomyces strains isolated from marine soft coral Sarcophyton convolutum have been demonstrated. Within fifty-one Streptomyces isolates evaluated for their hydrolytic enzymes and enzyme inhibitors productivities, six isolates showed the hyperactivities. Pharmaceutical metabolites productivities evaluated include enzymes (alkaline protease, L-asparaginase, L-glutaminase, tyrosinase, and L-methioninase) and enzyme inhibitors (inhibitors of α-amylase, hyaluronidase, β-lactamase, α-glucosidase, and β-glucosidase). These isolates were identified based on their morphological, biochemical, and genetic characteristics as Streptomyces sp. MORSY 17, Streptomyces sp. MORSY 22, Streptomyces sp. MORSY 25, Streptomyces sp. MORSY 36, Streptomyces sp. MORSY 45, and Streptomyces sp. MORSY 50. Moreover, in further evaluation, these strains exhibited wide spectrum of antimicrobial (against bacteria and fungi), antiviral (against hepatitis C virus), antibiofilm against biofilm-forming bacteria (methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas species), and anti-proliferative activities (against liver and colon carcinoma cell lines). The GC–MS analysis of the hyperactive strains MORSY 17 and MORSY 22 revealed the presence of different bioactive agents in the ethyl acetate extract of both strains.

Tumor-associated macrophages (TAMs) have been shown to both aid and hinder tumor growth, with patient outcomes potentially hinging on the proportion of M1, pro-inflammatory/growth-inhibiting, to M2, growth-supporting, phenotypes. Strategies to stimulate tumor regression by promoting polarization to M1 are a novel approach that harnesses the immune system to enhance therapeutic outcomes, including chemotherapy. We recently found that nanotherapy with mesoporous particles loaded with albumin-bound paclitaxel (MSV-nab-PTX) promotes macrophage polarization towards M1 in breast cancer liver metastases (BCLM). However, it remains unclear to what extent tumor regression can be maximized based on modulation of the macrophage phenotype, especially for poorly perfused tumors such as BCLM. Here, for the first time, a CRISPR system is employed to permanently modulate macrophage polarization in a controlled in vitro setting. This enables the design of 3D co-culture experiments mimicking the BCLM hypovascularized environment with various ratios of polarized macrophages. We implement a mathematical framework to evaluate nanoparticle-mediated chemotherapy in conjunction with TAM polarization. The response is predicted to be not linearly dependent on the M1:M2 ratio. To investigate this phenomenon, the response is simulated via the model for a variety of M1:M2 ratios. The modeling indicates that polarization to an all-M1 population may be less effective than a combination of both M1 and M2. Experimental results with the CRISPR system confirm this model-driven hypothesis. Altogether, this study indicates that response to nanoparticle-mediated chemotherapy targeting poorly perfused tumors may benefit from a fine-tuned M1:M2 ratio that maintains both phenotypes in the tumor microenvironment during treatment.

Triple-negative breast cancer is one of the most aggressive breast cancer. The first therapeutic option is chemotherapy, often based on anthracycline as doxorubicin. However, chemotherapy efficacy is limited in by the presence of P-glycoprotein (Pgp), a membrane transporter protein that effluxes doxorubicin, reducing its cellular accumulation and toxicity. Inhibiting Pgp activity with effective and non-toxic products is still an open challenge. In this work, we demonstrated that the natural product Glabratephrin (Glab), a prenylated flavonoid from Tephrosia purpurea with a unique chemical structure, increased doxorubicin accumulation and cytotoxicity in triple negative breast cancer cells with high levels of Pgp, characterized by both acquired or intrinsic resistance to doxorubicin. Glab also reduced the growth of Pgp-expressing tumors, without adding significant extra-toxicities to doxorubicin treatment. Interestingly, Glab did not change the expression of Pgp, but it reduced the affinity for Pgp and the efflux of doxorubicin, as suggested by the increased Km and the reduced Vmax. In silico molecular docking predicted that Glab binds two residues (phenylalanine 322, glutamine 721) localized in the transmembrane domains of Pgp, facing the extracellular environment. Moreover, site-directed mutagenesis identified glycine 185 as a critical residue mediating the reduced catalytic efficacy of Pgp elicited by Glab. We propose Glab as an effective and safe compound able to reverse doxorubicin resistance mediated by Pgp in triple negative breast cancers, opening the way to a new combinatorial approach that may improve chemotherapy efficacy in the most refractory and aggressive breast cancer.

In the current medical era, spirooxindole motif stands out as a privileged heterospirocyclic scaffold that represents the core for a wide range of bioactive naturally isolated products (such as Strychnofoline and spirotryprostatins A and B) and synthetic compounds. Interestingly, no much attention has been paid to develop spirooxindole derivatives with dual antioxidant and anticancer activities. In this context, a series of spirooxindoles 6a-p was examined for their anticancer effect towards HepG2 hepatocellular carcinoma and PC-3 prostate cancer cell lines. Spirooxindole 6a was found to be an efficient anti-proliferative agent towards both HepG2 and PC-3 cells (IC50 = 6.9 and 11.8 µM, respectively). Afterwards, spirooxindole 6a was assessed for its apoptosis induction potential in HepG2 cells, where its pro-apoptotic impact was approved via the significant elevation in the Bax/Bcl-2 ratio and the expression levels of caspase-3

The agricultural by-products are a significant source of health benefiting bioactive compounds. In this trend, the phenolic and flavonoid contents and functional properties of date palm seeds (DPS) and saw palmetto seeds (SPS) extracts were evaluated in this study. Considerable phenolic and flavonoid contents of 11.8, 7.75 mg GAE/g seed and 3.13, 1.1 mg CE/g seed were detected in DPS ethanol and SPS acetone extracts, respectively. The protocatechuic acid was the major compound in SPS and DPS extracts and represented 1.41 and 1.1 mg/g seed, respectively as well as similar phenolic compounds were detected using HPLC analysis. The DPS and SPS phenolic compounds possessed a strong antioxidant activity with IC50 values of 10.0, 2.2 and 2.0, 0.6 µg GAE/mL, using the DPPH and ABTS assays, respectively. The phenolic compounds of DPS and SPS extracts showed a potent and broad anti-bacterial activity against clinical multiple drug resistance bacterial strains with lower MIC values besides an effective anti-fungal activity against a number of human pathogenic fungal strains. Interestingly, in a model of LPS-induced inflammation in RAW 264.7 cells, DPS and SPS showed efficient anti-inflammatory effects to inhibit the iNOS protein expression and activity (NO release).

A polysaccharide characterized as galactomannan (GMann) with a molecular weight of 117.76 kDa was isolated from the aqueous extract of Caesalpinia gilliesii (C. gilliesii) seeds then assessed for antiproliferative potential against human hepatocellular carcinoma cell line (HepG2). Further, HCC was induced in Wister albino rats by Diethylnitrosamine (DEN) ip injection (200 mg/kg bw), and CCl4 orally (2 ml/kg bw) for two months then subjected to GMann orally treatment (2 mg/kg bw) for one month. In results, isolated GMann is constituted of sugars (89.99 ± 2.3%), moisture (6.89 ± 0.45%), ash (0.06 ± 0.2%), and protein (2.81%) and composed mainly of mannose and galactose in ratio M/G 3.79. In vitro study, data revealed a concentration-dependent potency of GMann to induce cell death of HepG2 cells with IC50 value of 0.375 µg/ml. Mechanistic studies revealed the potential of GMann to arrest cell cycle at G2/M phase with induction of apoptosis. Biochemical results in vivo showed a significant reduction in serum transaminases (ALT and AST) as well as hepatic malondialdehyde (MDA) and nitric oxide (NOx). Molecular analysis declared a significant down-regulation in mRNA gene expression of both nuclear factor kappa-B (NF-κB) and tumor necrosis factor (TNF-α). Furthermore, a significant down-regulation in the cellular oncogene-fos (C-fos) and marked up-regulation in Glycogen synthase kinase-3 (GSK-3β) level were observed. These results were supported with histopathological investigation. Whereas GMann improved inflammatory and apoptotic markers, it could be a promising new therapeutic agent for HCC suppression and this warrant further development as a possible drug candidate for HCC.

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with limited treatment options due to its heterogeneity and the lack of well-defined molecular targets. In our endeavour towards the development of novel anti-TNBC agents, herein we report a one-pot three-component synthesis of novel spirooxindoles 6a–p, and evaluation of their potential anti-proliferative activity towards TNBC MDA-MB-231 cells. Spirooxindoles 6a, 6e and 6i emerged as the most potent analogues with IC50 = 6.70, 6.40 and 6.70 µM, respectively. Compounds 6a and 6e induced apoptosis in MDA-MB-231 cells, as evidenced by the up-regulation of the Bax and down-regulation of the Bcl-2, besides boosting caspase-3 levels. Additionally, 6e displayed significant increase in the percent of annexin V-FITC positive apoptotic cells from 1.34 to 44%. Furthermore, spirooxindoles 6e and 6i displayed good inhibitory activity against EGFR (IC50 = 120 and 150 nM, respectively). Collectively, these data demonstrated that 6e might be a potential lead compound for the development of effective anti-TNBC agents.

One new naturally isoflavone compound, 5,7,2′,3′,4′ penta hydroxyl isoflavone-4′- O -β-glucopyranoside (1) was isolated from the aqueous methanol extract (AME) of Pulicaria undulata subsp. undulata , together with seven known compounds: kaempferol (2), kaempferol 3- O -β-glucoside (3), quercetin (4), quercetin 3- O -β-glucoside (5), quercetin 3- O -β-galactoside (6), quercetin 3,7-di OCH 3 (7), and caffeic acid (8). Their structures were established through chemical (acid hydrolysis) and spectral analysis (UV, NMR, and ESIM). The AME and some isolated compounds were evaluated as protective agents. Free radical scavenging using a microscaled 2,2-diphenyl-1-picrylhydrazyl assay was used to assess the direct antioxidant properties that were evaluated by the ability to protect murine Hepa1c1c7 liver cells against damage induced by the organic peroxide tert-butyl hydroperoxide. The neutral red uptake assay (NRU) was used to record the activity. Results of the 2,2-diphenyl-1-picrylhydrazyl assay recorded differential scavenging properties in ascending order: 5,7,2′,3′,4′ penta hydroxyl isoflavone-4′-O-β-glucopyranoside>quercetin>quercetin 3- O -galactoside>caffeic acid>quercetin 3,7-di-OCH 3 >kaempferol with 50% inhibitory concentrations of 3.9 μM, 7.5 μM, 11.4 μM, 12.2 μM, 78.1 μM, and 252.3 μM, respectively. The antioxidative potential reveals the potency of AME, quercetin, and quercetin 3,7-di-OCH 3 . The latter compound showed full protection at 100 μM (33 μg/mL) against the induced toxicant effect where the 50% effective concentration was calculated as 33.6±1.7 μM (11.1 μg/mL). In addition to quercetin, which was extensively shown previously as a cytoprotective agent, AME was less potent; it was capable of protecting 75% at 100 μg/mL with 50% effective concentration of 92.3±4 μg/mL. Moreover, the isolated flavonoids were found to be significantly chemosystematic markers.

BACKGROUND: Annona muricata (Soursop) has an antimicrobial activity toward various pathogenic microorganisms which support its ethnomedicinal for the treatment of many infectious diseases. AIM: Aim of the present study to evaluate the relation between antimicrobial activities of terpenoids extracted from different soursop parts with the isolated endophytic fungi. METHODS: Endophytic fungal species of pulp and peel of Annona fruit along with those of seeds were isolated. Salkowski test was used for qualitative screening of terpenoids in plant and the isolated endophytic Aspergillus niger strain SH3. RESULTS: Endophytic A. niger strain SH3 and Annona seed extract showed high terpenoid content indicated by the high intensity of reddish-brown colour. GC/Mass analysis revealed six compounds of terpenoids from endophytic A. niger strain SH3 extract and four compounds from seed extract with different retention times. The antimicrobial assay was performed using A. niger strain SH3 extract and Annona seed extract singly or in combinations against S. aureus, P. aeruginosa, E. coli and C. albicans. CONCLUSION: The results revealed the significant antimicrobial activity of both extracts. However, the combined extract showed some reduction in antimicrobial activity which could be attributed to the antagonistic effect exhibited by their constituents.

The alcoholic extract of Adhatoda vasica showed strong and reversible inhibition of the enzyme acetyl cholinesterase (AChE) with an IC50 = 294 μg/mL. Phytochemical study of the total alcoholic extract of A. vasica yielded four known compounds vasicine, vasicinone, vasicole and anisotine. Vasicine reversibly and competitively inhibited AChE with ki value 11.24 μM. On the other hand, rest of isolated alkaloids showed no/or weak inhibitory effect on AChE. Vasicine showed binding similarity to both galantamine and tacrine in the catalytic site. The obtained results support the multi-pharmacological properties of vasicine, which can be considered as a promising inhibitor for acetyl cholinesterase where it can be used directly or indirectly for the development of efficient anti-Alzheimer drug.

Medicinal plants from the Egyptian Sinai Peninsula are widely used in traditional Bedouin medicine to treat a range of conditions including cancer, and as such are a promising resource for novel anti-cancer compounds. To achieve scientific justification of traditional use and/or to recommend the use of those plants as medicinal herbs for cancer chemoprevention, a group of 11 Sinai plants of different species that belong to 3 families (Asteraceae, Lamiaceae, and Euphorbiaceae) were biologically screened for cancer preventive activity using the chemoprevention marker enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1). Among the fractions assayed, a solvent extract from Pulicaria incisa had potent NQO1 inducing activity. Further analysis of the mechanism of induction revealed the concentration-dependent stabilization of the transcription factor NF-E2 p45-related factor 2 (Nrf2) and a coordinate upregulation of the Nrf2-dependent enzymes NQO1, heme oxygenase 1 and glutathione S-transferase-Pi. These results establish P. incisa as a promising target for future phytochemical characterization for cancer preventive components.

Background Statistics on cancer incidence and mortalities indicate that this disease still has a fatal outcome for a majority of patients due to non-sufficient treatment. The options available for cancer treatment include chemotherapy, which still commands a leading position in clinical oncology. A major obstacle to successful chemotherapy is the development of cellular resistance to multiple structurally unrelated anticancer drugs. This phenomenon has been termed multidrug resistance (MDR), which occurs in a majority of cancer patients. MDR is mainly due to the overexpression of ABC transporters which extrude chemotherapeutic drugs outside of cancer cells. A plethora of synthetic chemosensitizers have been described during the past decades that block ABC transporter function to reverse their MDR. However, none of them reached clinical routine application as of yet. In this review, we highlight the potential of natural products derived from plants, marine organisms, fungi, and other sources as chemosensitizers to the targeted major ABC transporters (ABCB1, ABCC1, and ABCG2). Conclusion Natural compounds may serve as lead compounds for the development of novel ABC transporter inhibitors with improved pharmacological features that can be used as adjuvant therapy to enhance the efficacy of chemotherapeutic drugs against MDR.

Chemoprevention can be defined as a means of controlling cancer in which the incidence of the disease can be entirely prevented, slowed down, or reversed. Chemoprevention is acquiring great attention because it is a cost-effective alternative to cancer treatment, such as chemotherapy or radio-therapeutic programs, which should reduce the burden on local and global economies. There is increasing interest in studying the chemoprevention potentiality of natural compounds against cancer as a result of the reduced cancer risk in people who consume high amounts of phytochemicals in their diet. Chemoprevention may involve the interruption or reversal of the initiation and progression of the disease by setting targets with the goal of preventing end stage invasiveness and metastasis. The initiation stage of cancer can be stopped by preventing reactive oxygen species and/or carcinogen activity (i.e., scavenging free radicals or trapping carcinogens) or by inhibiting their metabolic activation, thereby suppressing their interaction with cellular macromolecular targets, such as DNA, RNA, and proteins. This can be achieved by inducing of a set of phase II detoxifying and antioxidant enzymes, such as the chemopreventive marker NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase (HO-1). NQO1 is a ubiquitous flavoenzyme that plays a crucial role in protecting cells from endogenous and exogenous oxidative stressors by catalyzing two- and four-electron reductions of these substrates to their hydroquinone forms. The expression of NQO1 in different tissues is regulated by antioxidant response elements (AREs) under both basal and oxidative stress conditions. NQO1 is known to be regulated by nuclear factor erythroid-derived related factor 2 (Nrf2), which belongs to the basic leucine zipper transcription factor family, and binds to AREs, leading to the expression of many cytoprotective and antioxidant genes. Since Nrf2 binds to AREs and regulates the expression and induction of NQO1, Nrf2 knockout causes a reduction in the constitutive expression of NQO1 and impairs its induction. Several vegetables and fruits, including blueberries, cocoa beans, cabbage, broccoli, and cauliflower, are among the most protective agents against cancer. This is specifically due to their high content of active phytochemicals, such as sulforaphanes, isothiocyanates, polyphenols, and flavonoids. Upon entering cells these chemicals can directly counteract free radicals and induce electrophilic stress signals that trigger proteins linked to diverse cellular signaling pathways. This capability involves activation of the NQO1 gene and other phase II detoxification genes by activating the Nrf2/Kelch-like ECH-associated protein (Keap1) complex system. This chapter reports the chemopreventive effect of dietary components or their phytochemicals by activating the Nrf2–Keap1/ARE pathway and inducing NQO1.

Diterpenoids salvimulticanol (1) and salvimulticaoic acid (2) together with known diterpenoid (3-6) were isolated from Salvia multicaulis. Structures were elucidated by spectroscopic techniques including HRESIMS as well as 1D-, and 2D-NMR. In-vitro cytotoxicity was assayed against human cancer cell lines. As several metabolites exhibited activity against drug-resistance lines, compounds were screened against a panel of human drug-sensitive and multidrug-resistant cancer lines. A proposed biosynthetic pathway for these new diterpenoids (1-2) as well as the cytotoxic structure-activity relationship of all identified compounds were discussed. Compound 1 and 6 showed the most potent cytotoxicity with IC50 11.58 and 4.13 towards leukemia cell lines CCRF-CEM and CEM-ADR5000, respectively.

Multidrug resistance (MDR) in various kinds of cancers represents a true obstacle which hinders the successes of most of current available chemotherapies. ATP-binding cassette (ABC) trasporter proteins have been shown to contribute to the majority of MDR in various types of malignancies. c-myc has recently been reported to participate, at least partly, in MDR to some types of cancers. This study aimed to test whether c-myc could play a role, solely or with coordination with other ABCs, in the resistance of HepG2 cells to doxorubicin (Dox). MDR has been induced in wild-type HepG2 and has been verified both on gene and protein levels. Various assays including efflux assays as well as siRNA targeting ABCB1 and c-myc have been employed to explore the role of both candidate molecules in MDR in HepG2. Results obtained, with regard to ABCB1 silencing on HepG2/Dox cells, have shown that ABCB1-deficient cells exhibited a significant reduction in ABCC1 expression as compared to ABCB1-sufficient cells. However, these cells did not show a significant reduction in other tested ABCs (ABCC5 and ABCC10) while c-myc silencing had no significant effect on any of the studied ABCs. Moreover, silencing of ABCB1 on HepG2 significantly increased fluorescent calcein retention in HepG2 cells as compared to the control cells while downregulation of c-myc did not have any effect on fluorescent calcein retention. Altogether, this work clearly demonstrates that c-myc has no role in MDR of HepG2 to Dox which has been shown to be ABCB1-mediated in a mechanism which might involve ABCC1.

Elevation of acetylcholinesterase enzyme (AChE) has been reported to be implicated in the etiology of Alzheimer disease (AD). One of the encouraged strategies to fight AD is the plant-derived inhibitors. Amaryllidaceae species are enriched source of alkaloids. The inhibitory properties of roots and bulbs of Pancratium maritimum L. against AChE have been previously reported. In the present study, the flowers of the wild Egyptian P. maritimum were subjected to screening assays to evaluate its potency as inhibitor to AChE. Besides, its antioxidant and cytotoxic properties were also addressed. The acetylcholinesterase inhibitory properties of P. maritimum ; total extract and its alkaloid mixture were examined using Ellman’s assay. The direct antioxidant examination was carried out using DPPH assay whereas the indirect was monitored by the ability to protect Hepa1c1c7 cells against the induced cytotoxicity produced by tert-butyl hydroperoxide (TBHP). The cytotoxic effect of the total extract and crude alkaloid mixture was evaluated against the human liver hepatoma cell line (HepG2). P. maritimum flowers showed significant inhibitory activity against AChE. The potency of the alkaloid mixture, representing 5.0% of the flowers weight (IC 50 ; 22.02 ± 0.59 μg/ml) was about fourfold of its total extract (IC 50 ; 97.67 ± 4.06 μg/ml). The total extract was able to protect about 33.4% of Hepa1c1c7 against the induced intoxication that carried by TBHP rather than the alkaloid mixture. Weak antioxidant and cytotoxic activities were recorded by both examined samples. Flowers of the Egyptian P. maritimum L. could be an enriched source of AChE inhibitors.

New sesquiterpenes tanacetolide A–C (1–3) were isolated from a Tanacetum sinaicum extract together with known compounds (4–10). The structures were elucidated on the basis of MS and NMR spectroscopic data. All the compounds were evaluated for the inhibition of inducible nitric oxide (NO) production in a mouse peritoneal macrophage system. Iso-seco-tanapartholide-3-O-methyl ether (4) produced potent inhibition of NO production (IC50 = 1.0 μM). At the protein expression level, 4 elicited concentration-dependant down-regulation of inducible nitric oxide synthase.

Hepatocellular carcinoma (HCC) is a hypervascular primary liver cancer characterized by rapid progression, besides, resistance to traditional chemotherapeutic agents. It has been shown that microRNAs play critical roles in regulation of tumor cell sensitivity to drugs through modulating the expression of genes involved in drug transport. The present study investigated whether restoration of miR-122 in HCC cells could alter the cell cycle distribution and the expression of multidrug resistance (MDR)-related genes (ABCB1, ABCC1, ABCG2 and ABCF2). After overexpression of miR-122 in HepG2 cells treated or untreated with doxorubicin doses, total RNAs and protein extracts were isolated for application of QRT-PCR and western blotting techniques. Moreover, cell cycle distribution was monitored by flow cytometry. Our results revealed that, the over expression of miR-122 in HepG2 cells treated or untreated with doxorubicin could modulate the sensitivity of cells to chemotherapeutic drug through downregulation of MDR-related genes, ABCB1 and ABCF2. Interpretation of cell cycle distribution revealed that, the anti-proliferative effect of miR-122 is associated with the accumulation of cells in G0/G1 phase. Moreover, treatment with miR-122 and doxorubicin resulted in high percentage of HCC cells in G0/G1 phase. Taken together, our findings revealed that, overexpression of miR-122 inhibited HCC cell growth by inducing cell cycle arrest and this arrest is associated with down-regulation of MDR-related genes.

Multidrug resistance (MDR) is a critical hindrance to the success of cancer chemotherapy. The main thing responsible for MDR phenotypes are plasma-membranes associated with adenosine triphosphate (ATP) Binding Cassette (ABC) drug efflux transporters, such as the P-glycoprotein (Pgp) transporter that has the broadest spectrum of substrates. Curcumin (CURC) is a Pgp inhibitor, but it is poorly soluble and bioavailable. To overcome these limitations, we validated the efficacy and safety of CURC, loaded in biocompatible solid lipid nanoparticles (SLNs), with or without chitosan coating, with the goal of increasing the stability, homogeneous water dispersibility, and cellular uptake. Both CURC-loaded SLNs were 5&ndash, 10-fold more effective than free CURC in increasing the intracellular retention and toxicity of doxorubicin in Pgp-expressing triple negative breast cancer (TNBC). The effect was due to the decrease of intracellular reactive oxygen species, consequent inhibition of the Akt/IKK&alpha, &beta, /NF-kB axis, and reduced transcriptional activation of the Pgp promoter by p65/p50 NF-kB. CURC-loaded SLNs also effectively rescued the sensitivity to doxorubicin against drug-resistant TNBC tumors, without signs of systemic toxicity. These results suggest that the combination therapy, based on CURC-loaded SLNs and doxorubicin, is an effective and safe approach to overcome the Pgp-mediated chemoresistance in TNBC.

An efficient, expeditious catalytic route for the synthesis of ethyl 6-amino-5-cyano-2-methyl-4-aryl-4H-pyran-3-carboxylates 2 was achieved via a three-component, one-pot reaction of malononitrile, ethyl acetoacetate, and various aromatic aldehydes in water as a solvent at room temperature. The key advantages are excellent yield, reaction time, and inexpensive catalyst. Also, cyclization of 4H-pyrans 2 to the corresponding 4H-pyrano[2,3-d]pyrimidines 3 using silica sulfuric acid in the presence of acetic anhydride was described. Some synthesized compounds exhibited promising antioxidant activities.

In continuation of our chemical investigation on some medicinal plants of the genus Achillea, chromatographic investigation of the methylene chloride/methanol (1:1) extract of the air-dried aerial part of Achillea biebersteinii Afan. (family Asteraceae) afforded a new natural monoterpene (2), in addition to two known sesquiterpenes (3 and 4). Compound 1 was isolated as light needle crystals. Structures were established on the basis of MS and NMR spectroscopic (1H, 13C, 1H-1H correlation spectroscopy, heteronuclear multiple-quantum coherence and heteronuclear multiple-bond correlation) data and in case of compound 1 were confirmed by X-ray analysis. All isolated compounds were examined for their anti-inflammatory activity to inhibit lipopolysaccharide-induced NO production in RAW264.7 macrophage cells. Compounds 3 and 4 produced a promising anti-inflammatory effect (76% and 80% inhibition, respectively). However, compounds 1 and 2 produced moderate inhibition of NO release recording a 41% and 36% inhibition of NO production, respectively.

Vibration can produce a wide variety of different effects to the operators. Farm equipment operators are usually exposed to whole-body vibration which transmitted via the seat or via the floor and feet. This vibration contributes to operator fatigue and can have a detrimental effect on job performance and safety. The objective of this study was to determine whether body mass index (BMI) influences the risk of low back pain (LBP) in a population exposed to whole body vibration (WBV). For this a survey conducted in nine farm machinery-servicing stations belong to the Ministry of Agriculture (MOA), Farm machinery station in Gemiza, Egyptian Project for improving the main crops production in Sakha, and the local sector of farm machinery during the years of 2008-2009 through periodic visits. Vibration measurements were performed according to ISO 2631-1, 1997. Two measurements were taken: stand height, and weight the results revealed that the tractor (Nasr model) which has no suspended seat and range of 60-65 horse power in the sample under study considers the highest equipment gives WBV data the frequency weighted RMS acceleration magnitude of the largest single orthogonal axis is in the vertical axis (Z) and also for VDV of weighted RMS acceleration. This constitutes a high risk on the labor body, followed by UTB tractor and rice combine. On the other hand, the WBV emission levels recorded during the harvesting by wheat combine and threshing tasks were low which constitute no risk on the labor body The results revealed that the highest number of injured labors was in the age group of (41-45) years (46.4%), followed by (46-50) years (28.6%), but the least number of injured labors was in the age group of (34-40) years (14.3%), and followed by (51-55) years (10.7%). Type of pain indicated that the highest number of pain was (47%) for temporary LBP, followed by (22.6%) for healthy body, and (8.3%) for chronic LBP. Results showed that there are significant differences between the different types of equipment during the variation of farm operations, significant correlation, and significant relationship between accidents factors.

Aims To investigate effect of metallic nanoparticles, silver (AgNPs) and gold nanoparticles (AuNPs) as antitumor treatment in vitro against human breast cancer cells (MCF-7) and their associated mechanisms. This could provide new class of engineered nanoparticles with desired physicochemical properties and may present newer approaches for therapeutic modalities to breast cancer in women. Materials and methods A human breast cancer cell line (MCF-7) was used as a model of cells. Metallic nanoparticles were characterized using UV-visible spectra and transmission electron microscopy (TEM). Cytotoxic effects of metallic nanoparticles on MCF-7 cells were followed by colorimetric SRB cell viability assays, microscopy, and cellular uptake. Nature of cell death was further investigated by DNA analysis and flow cytometry. Results Treatment of MCF-7 with different concentrations of 5-10nm diameter of AgNPs inhibited cell viability in a dose-dependent manner, with IC50 value of 6.28μM, whereas treatment of MCF-7 with different concentrations of 13-15nm diameter of AuNPs inhibited cell viability in a dose-dependent manner, with IC50 value of 14.48μM. Treatment of cells with a IC50 concentration of AgNPs generated progressive accumulation of cells in the S phase of the cell cycle and prevented entry into the M phase. The treatment of cells with IC50 concentrations of AuNPs similarly generated progressive accumulation of cells in sub-G1 and S phase, and inhibited the entrance of cells into the M phase of the cell cycle. DNA fragmentation, as demonstrated by electrophoresis, indicated induction of apoptosis. Conclusions Our engineered silver nanoparticles effectively inhibit the proliferation of human breast carcinoma cell line MCF-7 in vitro at high concentration (1000 μM) through apoptotic mechanisms, and may be a beneficial agent against human carcinoma but further detailed study is still needed.

An efficient, expeditious catalytic route for the synthesis of ethyl 6-amino-5-cyano-2-methyl-4-aryl-4H-pyran-3-carboxylates 2 was achieved via a three-component, one-pot reaction of malononitrile, ethyl acetoacetate, and various aromatic aldehydes in water as a solvent at room temperature. The key advantages are excellent yield, reaction time, and inexpensive catalyst. Also, cyclization of 4H-pyrans 2 to the corresponding 4H-pyrano[2,3-d]pyrimidines 3 using silica sulfuric acid in the presence of acetic anhydride was described. Some synthesized compounds exhibited promising antioxidant activities.

Background Egyptians recognized the healing power of herbs and used them in their medicinal formulations. Nowadays, “Attarin” drug shops and the public use mainly the Unani medicinal system for treatment of their health problems including improvement of memory and old age related diseases. Numerous medicinal plants have been described in old literature of Arabic traditional medicine for treatment of Alzheimer’s disease (AD) (or to strengthen memory). Methods In this study, some of these plants were evaluated against three different preliminary bioassays related to AD to explore the possible way of their bio-interaction. Twenty three selected plants were extracted with methanol and screened in vitro against acetylcholinesterase (AChE) and cycloxygenase-1 (COX-1) enzymes. In addition, anti-oxidant activity using DPPH was determined. Results Of the tested plant extracts; Adhatoda vasica and Peganum harmala showed inhibitory effect on AChE at IC50 294 μg/ml and 68 μg/ml respectively. Moreover, A. vasica interacted reversibly with the enzyme while P. harmala showed irreversible inhibition. Ferula assafoetida (IC50 3.2 μg/ml), Syzygium aromaticum (34.9 μg/ml) and Zingiber officinalis (33.6 μg/ml) showed activity against COX-1 enzyme. Potent radical scavenging activity was demonstrated by three plant extracts Terminalia chebula (EC50 2.2 μg/ml), T. arjuna (3.1 μg/ml) and Emblica officinalis (6.3 μg/ml). Conclusion Interestingly, differential results have been obtained which indicate the variability of the mode of actions for the selected plants. Additionally, the reversible interaction of A. vasica against AChE and the potent activity of F. assafoetida against COX-1 make them effective, new and promising agents for treatment of AD in the future, either as total extracts or their single bioactive constituents.

Background The Egyptian government is considering embarking on a new wave of health sector reform. Although primary care is seen as central to the anticipated reforms, little is known about the current morbidity and utilization patterns in Egyptian publicly funded primary care. We conducted this survey study of patient encounters to describe the demographic characteristics of patients attending publicly-funded primary care practices, the relative frequency of conditions encountered in these practices, and the rates of drug prescription, investigation and referral. Method Cross-sectional survey of twelve primary care practices and 2458 patient consultations. Additional secondary data were collected from five of the twelve practices for preventive services provided at these practices i.e. immunizations, family planning and ante-natal care. Results 54% of the attendances were for people below the age of twenty, of which 54% were females. In patients above the age of twenty, women accounted for 73% of consultations. Upper respiratory tract infection was the most common reason for encounter, accounting for 24% of the presentations, followed by gastroenteritis (10%), intestinal parasites (5%), and lower respiratory tract infections (5%). Over 97% of patients were prescribed at least one drug, whereas investigation and referral rates were low (15% and 5% respectively). When the analysis was repeated for practices where data on both curative and preventive services were available (5 practices and 2146 consultations), substantial proportions of patients were found to seek care for immunizations (25%), family planning (12%), and ante-natal care (11%). Conclusion Most patients utilizing primary care practices in Egypt seek care for minor and preventive services with relatively few consultations for more serious conditions. There is also a pattern of prescribing drugs to most primary care patients which may reflect over-prescribing by primary care doctors.

Capparis cartilagineaandC. desertigrowing in Egypt were investigated for their glucosiolates and rutin content. FromCapparis cartilagineafour isothiocynates were isolated and identified using GC and EI/MS techniques. These compounds were butyl isothiocyanate (1), 6-methylsulphonylhexyl isothiocyanate (2), 7-methylsulphonylheptyl isothiocyanate (3) and 5-benzylsulphonyl-4-pentenyl isothiocyanate (4). In addition to compounds (1) and (2), two other compounds were isolated and identified fromCapparis deserti. These compounds are 3-methylthiopropyl isothiocyanate (5) and [11-(2-butenylthio)6-undecenyl isothiocyanate] (6). Compounds (1), (2), (5) and (6) are reported in this study for the first time fromCapparis deserti. The main flavonoid component in the studied species was isolated and identified as rutin by comparing the data with those reported. Also, quantitative evaluation of rutin in the two species was carried out by TLC-densitometric analysis. The antioxidant activity was done using diphenylpicrylhydrazyl (DPPH) radical scavenging method. The butanol fraction fromC. cartilagineaandC. desertishowed the highest antioxidant properties.