Tosyl-carrageenan/alginate composite adsorbent for removal of Pb2+ ions from aqueous solutions.

The current study effectively designed novel cross-linked tosyl-carrageenan/alginate (Ts-Car/Alg) beads to remove Pb2+ ions from their aqueous solutions. To confirm the structure of the produced matrix, characterization methods such as XRD, SEM, FTIR, and EDX were used. Batch experiments were employed in order to further evaluate the adsorption efficiency of Pb2+ ions. Additionally, various variables, including contact time, solution pH, adsorbent dosage, and initial concentration of Pb2+ ions were investigated using atomic absorption. The results of this study showed that the adsorption equilibrium increased as Pb2+ ions concentration increased at pH = 5.3 after a contact time of 120 min, with 0.3 g of Ts-Car/Alg that having the best adsorption capacity at 74 mg/g. The adsorption progression was further examined using the kinetic and isothermal models. With a correlation coefficient of 0.975, the Freundlich model was thought to better fit Pb2+ ions adsorption from the isotherm investigation. Also, the adsorption kinetics were investigated using a pseudo-second-order model with 1/n ratio of 0.683. This Ts-Car/Alg adsorbent is regarded as an effective candidate to be used for water treatment because the reusability process of produced beads was successfully completed twice, and the adsorbent maintained its ability to remove Pb2+ ions. The prepared Ts-Car/Alg beads are therefore excellent candidates to be used as potent Pb2+ ions adsorbents from their aqueous solutions. The Ts-Car/Alg beads' regeneration and reusability investigation for the removal of heavy metal ions was completed in at least two successful cycles.

EGFR and PI3K/m-TOR inhibitors: design, microwave assisted synthesis and anticancer activity of thiazole-coumarin hybrids.

A series of thiazoline and thiazolidinone-based 4-hydroxycoumarin derivatives were synthesized using both conventional synthesis procedures and microwave-assisted techniques. The new compounds were evaluated for their cytotoxic effect against three human cancer cell lines; MCF-7, HCT-116 and HepG2 and one normal human cell line (BJ-1). The promising anti-proliferative compounds 2a, 2b, 6a and 6b were assessed for inhibiting EGFR and PI3K/mTOR. Compound 6a showed the highest inhibition activity towards the signaling pathway. The apoptotic effect and cell cycle arrest potential of derivative 6a were examined. Moreover, the molecular docking, physicochemical properties and pharmacokinetic parameters of the promising compound were investigated, as well.

Impact of Nano-Bromocriptine on Egg Production Performance and Prolactin Expression in Layers.

The current study aimed to investigate the potential use of nano-bromocriptine in improving the laying performance of late laying hens by modulating the prolactin gene expression. A total of 150 NOVOgen brown laying hens aged 70 weeks were randomly allocated into three groups of 50 birds each. The first group was kept as a control, while the second and the third groups were treated with bromocriptine and nano-bromocriptine, respectively, at a dose of 100 µg/kg body weight per week. The pause days, egg production, feed per dozen egg, and Haugh unit were determined on a monthly basis. Also, the relative prolactin gene expression in the pituitary gland was quantified using qPCR and the number of the ovarian follicles was determined after slaughtering at the 84th week of age. It was found that nano-bromocriptine and bromocriptine improved egg laying performance with minimal pause days, reduced feed per dozen egg, and depressed the relative prolactin gene expression; however, nano-bromocriptine treatment was significantly effective compared to bromocriptine. In conclusion, nano-bromocriptine might be beneficial for elongating sequences and reducing pauses.

Grafted carrageenan: alginate gel beads for catalase enzyme covalent immobilization.

A new matrix formulation was devised for catalase immobilization. Carrageenan-alginate beads different ratios were developed and soaked into different ratios of CaCl2-KCl as a hardening solution. The best formulation for loading capacity was selected, treated with polyethylene imine followed by glutaraldehyde and further studied. The best concentration of catalase for immobilization was 300U/ml and the best loading time was 6 h. The catalytic properties increased after immobilization and the immobilized catalase achieved optimum activity at a temperature range of 30-50 °C that was compared to the optimum activity of free catalase which occurred at 40 °C. Higher catalytic activity of immobilized catalase occurred at alkaline pHs than the free one which achieved optimum catalytic activity at neutral pH. A comparison between the kinetic parameters of immobilized and free catalase showed variation. The K M and Vmax of the immobilized catalase were 2.4 fold and six times higher than those of free catalase. The results of the study indicate that the formulated matrix can be used as a good matrix for catalase enzyme in various industrial applications.

Chitosan and chitosan nanoparticles as adjuvant in local Rift Valley Fever inactivated vaccine.

The present study aimed to improve the potency of inactivated Rift Valley Fever Virus (RVFV) vaccine using chitosan (CS) or chitosan nanoparticles (CNP) as adjuvants. Chitosan nanoparticles were prepared by ionic gelation method. Rift Valley Fever Virus (RVFV) inactivated antigen was loaded on CS and CNP to form two vaccine formulations, RVFV-chitosan nanoparticles based vaccine (RVFV-CNP) and RVFV chitosan based vaccine (RVFV-CS). Five groups of mice were used in this study, each group was injected with one of the following: phosphate buffer saline (group1 G1), RVFV-CNP (G2), (RVF-CS) (G3), RVFV-Alum based vaccine (RVFV-Alum) (G4) and adjuvant free RVFV inactivated antigen (RVFV-Ag) (G5). The immunization was performed twice with 2 weeks interval. The results showed that, RVFV-CNP vaccine enhanced strongly the phagocytic activity of peritoneal macrophage (PM), neutralization antibodies titer against RVFV and IgG values against RVFV nucleoprotein than other vaccine formulations did. In addition, the RVFV-CNP and RVF-CS vaccines upregulate the gene expression of IL-2, IFN-γ (which promote cell mediated immunity) and IL-4 (which promote humeral immunity), while RVFV-Alum vaccine upregulate the gene expression of IL-4 only. These findings indicated that CS and CNP were comparable to the alum as adjuvant in efficacy but superior to it in inducing cell-mediated immune response and might be a candidate adjuvant for inactivated RVFV vaccine.

Synthesis and Characterization of Macrocyclic Chiral Tröger's Base Phenhomazine Candidates as Anticancer Agent.

1,4,7,10-Tetraoxa[10](2,8)trögerophane 5 was synthesized from its corresponding precursors. Heating of 2 with p-nitrophenoxide afforded bis(p-nitrophenyl)ether 3, which was treated with hydrazine hydrate to give bis(p-aminophenyl)ether 4. Treatment of 4 with paraformaldehyde and triflouroacetic anhydride gave trögerophane 5. Reaction of 5 with trifluroacetic anhydride afforded phenhomazine derivative 6, which was treated with potassium carbonate to afford tetrahydrophenhomazine 7. Finally, reaction of 7 with phenacylchloride, bromoacetic acid, or ethyl bromoacetate in the presence of triethyl amine under reflux, afforded the corresponding macrocyclic compounds 8, 9 and 10, respectively. The synthesized trögerophane,precursors and its newly synthesized phenhomazines derivatives were screened for anticancer activity. Results revealed that 1,4,7,10-tetraoxa[10](2,8)trögerophane had a promising selectivity towards colon cancer cell line with an IC50 of 92.7 µg/ml.

Synthesis, Antimicrobial and Antitumor Evaluations of a New Class of Thiazoles Substituted on the Chromene Scaffold.

BACKGROUND & OBJECTIVE: A new series of thiazoles substituted on the chromene scaffold were prepared by facial approaches starting from (E)-1-(2,3-Dihydrochromen-4-ylidene)thiosemicarbazide derivatives (2a,b). The thiosemicarbazides (2a,b) were reacted with a series of α-halo carbonyl compounds to give the corresponding rhodanine analogues and reacted also with C-acetyl-or Cethoxy- N-hydrazonoyl chlorides to afford the corresponding tri- and tetra-substituted hybrid hydrazinyl thiazole substituted chromenes. METHODS: The newly synthesized compounds were screened for their in vitro antimicrobial and antitumor activities by agar diffusion method and MTT assay, respectively. RESULTS: The results of the antimicrobial activity revealed that some of the new compounds exhibited excellent activity against pathogenic microorganism; Candida albicans compared with Ciprofloxacin and nystatin, as the reference drugs. All of the tested compounds exhibited significant cytotoxic activities comparable to that of the reference drug; Doxorubicin® (on HCT116 (colorectal carcinoma human cell line).

Novel method of preparation of tricarboxylic cellulose nanofiber for efficient removal of heavy metal ions from aqueous solution.

2,3,6­Tricarboxy cellulose nanofiber (TPC-CNFs) was prepared by 2,2,6,6-tetramethylpiperidine­1­oxyl (TEMPO) oxidation of dissolving cellulose pulp (selective at C-6) followed by periodate-chlorite oxidation (selective on C-2 and C-3). Characterization of the prepared samples were carried out using, atomic force microscope (AFM), carboxylate content determination, FTIR spectroscopy, X-ray diffraction and light transmittance spectra. Also, the mechanical properties of TEMPO-oxidized of cellulose nanofiber (T-CNFs) and TPC-CNFs with and without polyamide-amine-epichlorohydrin crosslinker (PAE) films were determined which the tensile strength were 8.19, 12.43 and 20.5 MPa and elastic moduli of 1814, 1097 and 1150 MPa respectively. Tricaboxy cellulose nanofiber was developed as a novel adsorbent of heavy metal ions. Removal of heavy metals such as Cu2+, Ca2+ and Pb2+ from aqueous solution was carried out and the adsorption efficiencies were analyzed. On the other hand, the effect of the addition of the crosslinking agent to CNFs and the carboxylate contents of CNFs were investigated.

Design, Synthesis and In-vivo Anti-inflammatory Activity of New Celecoxib Analogues as NSAID.

BACKGROUND: A new series of Celecoxib analogues were easily synthesized via reactions of 4-(2-(1-chloro-2-oxopropylidene)hydrazinyl)benzene sulfonamide (1) with active methylene compounds and dialkyl malonate. In addition, compound 1 was reacted also with thiourea derivatives and thiosemicarbazone derivatives to afford thiazole derivatives 9 and 11, respectively. Furthermore, triazolo pyrimidine derivatives 13 were prepared via reaction of compound 1 with pyrimidine thione derivatives. The structures of the new synthesized compounds were assigned by elemental analysis and spectroscopic data. The new analogues were screened for their in vivo anti-inflammatory activity using carrageenan-induced paw edema method. CONCLUSION: They showed moderate to good in vivo anti-inflammatory effects. Compounds 1, 6 and 11b were the most active compounds that reduced the paw edema induced by carrageenan by 12.25 %, 12.96 % and 12.97% respectively, as compared to the Indomethacin that inhibited the oedema volume by 7.47 %.

Synthesis, Anticancer Screening and Molecular Docking Studies of New Heterocycles with Trimethoxyphenyl Scaffold as Combretastatin Analogues.

BACKGROUND: In this study, synthesis, molecular docking and anticancer screening of new series of substituted heterocycles with trimethoxy phenyl scaffold as Combretastatin analogues were described. Substituted pyridines were synthesized via the reaction of (E)-3-(dimethylamino)-1-(3,4,5- trimethoxyphenyl)prop-2-en-1-one (2) with active methylene reagents. Substituted pyrimidines were prepared by the reaction of the enaminone (2) with heterocyclic amines and 6-amino thiouracil. Furthermore, a series of pyrazoles substituted with trimethoxyphenyl scaffold were prepared by the reaction of the enaminone 2, with selected examples of hydrazonoyl halides. CONCLUSION: The cytotoxic effect of the newly compounds was evaluated against HePG-2, HCT-116, MCF-7 and PC3 cancer cell lines. Among the new products, compounds 2, 3, 7 and 10 were found to exhibit promising results as anticancer agents. The IC50 values of 2, 3 and 7 were 54.6, 77.4 and 47.4 on PC3 respectively. Also, compound 2 had IC50 28.06 on MCF7. Moreover, the selectivity index indicated that compounds 2 and 3 are safe.

Synthesis and Antimicrobial Evaluation of a New Series of Heterocyclic Systems Bearing a Benzosuberone Scaffold.

A series of novel benzosuberone derivatives were synthesized and evaluated as antimicrobial agents by using substituted benzosuberone derivatives 1a,b as starting materials. Treatment of 1a,b with phenyl isothiocyanate in dimethylformamide was followed by treatment with cold HCl solution to afford the thioamides 4a,b, which was reacted with methyl iodide to obtain methylated products 5a,b. Cyclocondensation of 4a,b with chloroacetone 6 and phenacyl chloride 7 gave the corresponding thiophene derivatives 9a-c. Reaction of 4a,b with C-acetyl-N- arylhydrazonoyl chlorides 14a and 14b in boiling EtOH in the presence of triethylamine, afforded the corresponding 1,3,4-thiadiazoline derivatives 16a-d. The thioamides 4a,b were reacted with C-ethoxycarbonyl-N-arylhydrazonoyl chlorides 18a,b which afforded 1,3,4-thiadiazoline derivatives 19a-d. The benzosuberones 1a,b were treated with 3-mercaptopropanoic acid to give compounds 21a,b, which were cyclized to tricyclic thiopyran-4(5H)-one derivatives 22a,b. The latter compounds 22a,b were reacted with 3-mercaptopropanoic acid to give compounds 23a,b, which were cyclized tetracyclic ring systems 24a,b. Finally, compounds 24a,b were oxidized using hydrogen peroxide under reflux conditions to afford the oxidized form of the novel tetracyclic heterogeneous ring systems 25a,b. The newly synthesized compounds were screened for antimicrobial activities. The structures of new compounds were characterized by ¹H-NMR, 13C-NMR, IR, and EI-MS.

Synthesis and Anticancer Properties of Silver(I) Complexes Containing 2,6-Bis(substituted)pyridine Derivatives.

Several new 2,6-bis(substituted)pyridine ligands and 2,6-bis(substituted)pyridine Ag(I) nitrate complexes were synthesized and characterized spectroscopically. The newly synthesized ligands include pyridine-2,6-bis(3-oxopropanenitrile) (1), pyridine-2,6-bis(2-cyano-N-phenyl-3-oxopropanethioamide) (2), and pyridine-2,6-bis((E)-2-(2-phenylhydrazono)-3-oxopropanenitrile) (3). The newly synthesized ligands and silver(I) complexes were evaluated for their in vitro anticancer activity against four human cancer cell lines including hepatocellular carcinoma (HePG2), lung adenocarcinoma (A549), colon carcinoma (HT29), and breast adenocarcinoma (MCF7). Most of the newly synthesized silver(I) complexes exhibited better activity than the ligands, and the results have been compared with doxorubicin as a reference drug.

Synthesis and antimicrobial evaluation of some new cyclooctanones and cyclooctane-based heterocycles.

The versatile synthon (E)-2-((dimethyl amino)methylene)cyclooctanone (2) was used as a key intermediate for the synthesis of cyclooctanones and cyclooctane-based heterocycles with pyrazole, isoxazole, pyrimidine, pyrazolopyrimidine, triazolopyrimidine and imidazopyrimidine derivatives via its reactions with several nitrogen nucleophiles. The newly synthesized compounds were screened in vitro for their antimicrobial activity against pathogenic microorganisms (Listeria monocytogenes, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans). Most of the tested compounds showed moderate to high antibacterial and antifungal effects against the tested pathogenic microorganisms. Among the synthesized compounds, 2-((p-sulfonamidophenyl)methylene)cyclooctanone (5) showed excellent activity against Listeria monocytogenes.

Synthesis of new functionalized 3-substituted [1,2,4]triazolo [4,3-a]pyrimidine derivatives: potential antihypertensive agents.

A convenient synthesis of a series of thiosemicarbazide, 1,3,4-oxadiazole, 1,3,4-thiadiazole, thiazole, 1,2,4-triazole, pyrazole and dioxoisoindoline derivatives incorporating 1,2,4-triazolo[4,3-a]pyrimidine via the reaction of the readily accessible 1,5-dihydro-5-oxo-1.7-diphenyl-1,2.4-triazolo[4,3-a]pyrimidine-3-carbohydrazide (2) with the appropriate reagents is described. The newly synthesized compounds were found to possess antihypertensive and diuretic activities compared to captopril and furosemide as reference controls, respectively.

Design, synthesis and structure-activity relationship study of novel pyrazole-based heterocycles as potential antitumor agents.

The versatile hitherto unreported 3-[(E)-3-(dimethylamino)acryloyl]-1,5-diphenyl-1H-pyrazole-4-carbonitrile (3) was prepared via the reaction of 3-acetyl-1,5-diphenyl-1H-pyrazole-4-carbonitrile (1) with dimethylformamid-dimethylacetal (DMF-DMA). The latter product and 3-((E)-3-morpholin-4-yl-acryloyl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile (4) underwent regioselective 1,3-dipolar cycloaddition with nitrilimines to afford the corresponding pyrazole derivatives. In vivo anti-estrogenic activity and acute toxicity after single oral dose of the newly synthesized compounds were evaluated. In vitro disease-oriented primary antitumor screening utilizing 14 cell lines of breast and ovarian tumor subpanels has been also carried out. All tested compounds showed anti-estrogenic properties equipotent or superior to the reference drug, letrozole. 3-[3-(4-Cyano-1,5-diphenyl-1H-pyrazole-3-yl)-1-(4-methylphenyl)-1H-pyrazole-4-carbonyl]-1,5-diphenyl-1H-pyrazole-4-carbonitrile (27c) and 3-(3-acetyl-1-phenyl-1H-pyrazole-4-carbonyl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile (8a) showed a significant cytotoxic activity in a nanomolar range against certain types of breast and ovarian tumors with tolerable toxicity.

Synthesis and structure-activity relationship studies of pyrazole-based heterocycles as antitumor agents.

Several 4-cyano-1,5-diphenylpyrazoles attached to different heterocyclic ring systems at position 3 were synthesized starting from ethyl 4-cyano-1,5-diphenyl-1H-pyrazole-3-carboxylate 1. The newly synthesized compounds were tested in vivo for their anti-estrogenic effects and evaluated in vitro for their cytotoxic properties against estrogen-dependent tumors. 3-(5-Mercapto-1,3,4-oxadiazole-2-yl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile 13 revealed the highest cytotoxic activity with a GI(50) value equal to 40 nM against the IGROVI ovarian tumor cell line. It also showed an anti-estrogen activity 1.6 more effective than the reference drug, in addition to a high tolerable dose. 3-(5-(Methylthio)-4-phenyl-4H-1,2,4-triazol-3-yl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile 7 was found to have the highest anti-estrogenic activity, while 1,5-diphenyl-3-[5-(phenylamino)-1,3,4-thiadiazol-2-yl]-1H-pyrazole-4-carbonitrile 11 showed the lowest activity. The oral LD(50) values revealed that most of the tested compounds are relatively nontoxic.

Cytotoxic, antioxidant activities and structure activity relationship of some newly synthesized terpenoidal oxaliplatin analogs.

The terpenoidal oxaliplatin derivatives (6) and (12) were newly synthesized using 2beta,3alpha-dihydroxy-11-oxo-18beta-olean-12-ene-30-oic acid (1) and 2alpha,2beta-dihydroxy-18beta-ursan-12-ene-28-oic acid (7) as starting materials. The synthesized compounds were evaluated for their cytotoxicity and antioxidant activities and were compared to Oxaliplatin and vitamin C as positive controls. Some of the compounds exhibited better cytotoxicity and antioxidant activities than the reference controls. The detailed synthesis, spectroscopic data, toxicity (LD(50)) and pharmacological screening for the synthesized compounds were reported.