New bipyridine derivatives were synthesized using 2-oxo-4-(pyridin-3-yl)-6-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile 1a. Terpyridine derivatives were synthesized using 2-oxo-4-(pyridin-3-yl)-6-(pyridin-4-yl)-1,2-dihydropyridine-3-carbonitrile 1b as the starting material. Alkylation of compounds 1a, b gave the alkyl derivatives 2a, b which converted into acetohydrazides 3a,b. Treating the acetohydrazides with ethyl cyanoacetate obtained 2'-[2-(3,5-dioxopyrazolidin-1-yl)-2-oxoethoxy]-6'-(thiophen-2-yl)-3,4'-bipyridine-3'-carbonitrile4a and 6'-[2-(3,5-dioxopyrazolidin-1-yl)-2-oxoethoxy]-(3,4':2',4''-terpyridine)-5'-carbonitrile 4b. While treatment of 3a, b with ethyl benzoylacetate obtained the carbonitrile derivatives 2'-(2-oxo-2-(5-oxo-3-phenyl-4,5-dihydropyrazol-1-yl)ethoxy)-6'-(thiophen-2-yl)-3,4'-bipyridine-3'-carbonitrile 5a and 6'-[2-oxo-2-(5-oxo-3-phenyl-4,5-dihydropyrazol-1-yl)ethoxy]-(3,4':2',4''-terpyridine)-5' carbonitrile 5b. Treating compounds 3a, b with two aromatic aldehydes (3,4-dihydroxy benzaldehyde, 4-chlorobenzaldehyde) obtained Schiff bases 6a-d. Finally, the treatment of 3a, b with p-toluenesulfonyl chloride (Tosyl chloride) obtained the corresponding benzene sulfonohydrazide 7a, b. IR, 1HNMR, 13CNMR, MS, and elemental analysis confirmed the of the synthesized compounds. The anticancer activity of the compounds was investigated against breast cancer MCF-7 cell line. Compound6b demonstrated the strongest cytotoxic activity among the tested compounds and was more active than the reference drug 5-fluorouracil (5-FU). Thus, it was subjected to further investigations, where its effect on the cell cycle distribution in the MCF-7 cell line, its ability to inhibit topoisomerase II, the level of caspase-3/7 green flow cytometry assay was investigated. Also, molecular operating environmental docking (MOE) was studied and found that the inhibition efficiency could be organized as follows (S, Kcal/mol) values: 5b > 6d > 3a > 3b > 6b; while compound 5a did not show any interaction data belonging to the shaped complex with 1cca. Hence, most of the synthesized compounds can be used as anticancer and anti-oxidant agents

As an extension of our research on the chemistry of heterocyclic compounds of great effectiveness and biological importance, we focused our interest on phenazines. In this review article, we reviewed the synthesis of phenazines, either chemically or biologically and, also reported the different reactions of them and some of their biological importance, such as antimicrobial activity, anti-oomycete activity, genotoxicity and, cytotoxicity. Here, we also reported some other uses such as using them in the development of electrochemical sensors and biosensors and using them for dye-sensitized solar cells (DSSCs).

Intelligent food wrapping materials have sparked interest in preserving food from spoilage until it reaches to consumers. Sufficient moisture from the air can be picked up by the food to encourage microorganism’s growth. One of the most significant matters in food chemistry is bright packaging which enables the researchers to keep an eye on the quality of food. In the light of these factors, the researchers made long efforts to synthesize responsive-stimuli chitosan hydrogels from shrimp shell preparative chitosan which cross-linked with different weights of 1,6-diisocyanatohexane in refluxing 1% glacial acetic acid. Alternatively, the newly harvesting hydrogels were screened as meat and chicken smart packaging because they were soft, biodegradable, and flexible instead of plastic packaging that is nonbiodegradable and causes environmental pollution. The flexibility enabled hydrogels to be folded around the meat and chicken pieces. The synthesized hydrogels were confirmed by Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, and thermogravimetric analyses.

BACKGROUND AND OBJECTIVE:Due to the well-documented anti-proliferative activity of 2-thiohydantoin incorporated with pyrazole, oxadiazole, quinazoline, urea, β-naphthyl carbamate and Schiff bases, they are noteworthy in pharmaceutical chemistry.METHODS:An efficient approach for the synthesis of a novel series of 2-thiohydantoin derivatives incorporated with pyrazole and oxadiazole has proceeded via the reaction of the acyl hydrazide with chalcones and/or triethyl orthoformate. Schiff bases were synthesized by the reaction of the acyl hydrazide with different aromatic aldehydes. Moreover, Curtius rearrangement was applied to the acyl azide to obtain the urea derivative, quinazoline derivative, and carbamate derivative.RESULTS:The synthesized compounds structures were discussed and confirmed depending on their spectral data. The anticancer activity of these heterocyclic compounds was evaluated against the breast cancer cell line (MCF-7), where they showed variable activity. Compound 5d found to have a superior anticancer activity, where it has (IC50 = 2.07 ± 0.13 μg/mL) in comparison with the reference drug doxorubicin that has (IC50 = 2.79 ± 0.07 μg / mL). Then compound 5d subjected to further studies such as cell cycle analysis and apoptosis. Apoptosis was confirmed by the upregulation of Bax, downregulation of Bcl-2, and the increase of the caspase 3/7percentage.CONCLUSION:Insertion of pyrazole, oxadiazole and, quinazoline moieties with 2-thiohydantoin moiety led to the enhancement of its anti-proliferative activity. Hence they can be used as anticancer agents.

On account of the interesting pharmacological properties of 2-thiohydantoin derivatives, and other purposes such as textile printing, catalysts for polymerizations, their uses in the production of resins and plastics, they have been the subject of chemical and biological studies. In this review article, we focused our interest on the most important methods for the synthesis of 2-thiohydantoin derivatives, different reactions and different applications of them. We explored their antitumor, antimicrobial, antidiabetic, anticonvulsant activities, their utilities in treatment of vascular dysfunction and, using them as an inhibitor of fatty acid amide hydrolase.

Background: Quinolones are a significant group of nitrogen heterocyclic compounds that exist in therapeutic agents, alkaloids, and synthetic small molecules that have important biological activities. A wide range of quinolones have been used as antituberculosis, antibacterial, anti-malarial, antifungal, anticonvulsant, anticancer agents and urease inhibitors. Methods: Ethyl 3,3-disubstituted-2-cyano propionates containing hybride quinolones derivatives were synthesized by the reaction of 1-amino-7-hydroxy-4-methylquinolin-2(1H)-one and its dibromo derivative with α, β-unsaturated carbonyl in ethanol. Results: A novel series of hybrid 2-quinolone derivatives was designed and synthesized. The compounds structures were confirmed using different spectroscopic methods and elemental analysis. The cytotoxic activities of all the compounds were assessed against HepG2 cell line in comparison with doxorubicin as a standard drug. Conclusion: Most compounds revealed superior anti-proliferative activity than the standard. Compound 4b, is the most active compound (IC50 = 0.39mM) compared with doxorubicin (IC50 = 9.23mM). DNA flow cytometric analysis of compound 4b showed cell cycle arrest at G2/M phase with a concomitant increase of cells in apoptotic phase. Dual annexin-V/ propidium iodide staining assay of compound 4b revealed that the selected candidate increased the apoptosis of HepG-2 cells more than control.

A series of new metal complexes were synthesized in both bulk and nano size using green methods, starting with the reaction of (E)‐N′‐[(E)‐2‐bromobenzylidene]‐4‐oxo‐4‐(piperidin‐1‐yl)but‐2‐enehydrazide with thiosemicarbazide and different metal halides such as CuI·2H2O, CuCl2·2H2O, CoCl2·2H2O, and ZnCl2·2H2O, and metal nitrate such as Ga(NO3)3·2H2O. Structures of these metal complexes were confirmed using different spectroscopic methods, elemental analysis, electronic spectra, and microanalytical methods (scanning electron microscopy and transmission electron microscopy) for nano complexes. The distorted octahedral geometry for all complexes was suggested based on magnetic moments and electronic spectral studies. The cytotoxic activity of the compounds was investigated against human hepatocellular carcinoma (HepG2) and human colorectal carcinoma (HCT‐116) cell lines. Most tested compounds had higher inhibitory activity than the standard vinblastine drug. Interestingly, the nano‐sized Ga(III) complex 11 was the most potent compound against the two tested cell lines, with 50% inhibitory concentration (IC50) of 2.56 μg/mL for HepG2, compared with the reference drug vinblastine (IC50 15.6 μg/mL), and IC50 4.64 μg/mL for HCT‐116, compared with the standard (IC50 13.9 μg/mL). The bioassay results helped us identify new potent and selective anticancer agents.

A novel series of substituted 2-thiohydantoin incorporated with benzoimidazole, pyrazole, triazole and/or benzoxazole moieties has been synthesized using (E)-3-[1-(4-bromophenyl)ethylideneamino]-2-thioxoimidazolidin-4-one 1 as the key starting material. The key material 1 also, reacted with an acetic anhydride, aromatic aldehydes, secondary amines, formaldehyde and triethyl orthoformate to give the corresponding acetyl, chalcone, Mannich bases and ethoxymethylene derivatives, respectively. The structures of the novel compounds were confirmed by spectral data and elemental analysis. The cytotoxic activity of all synthesized compounds was assessed in vitro against human hepatocellular cancer cell line (HePG-2) and breast carcinoma cell line (MCF-7). The bioassay results revealed that compound 14 has the best activity against HePG-2 cell line (IC50 = 2.33 μg/mL), while compound 5 has the best activity against MCF-7 cell line (IC50 = 3.98 μg/mL).

A new series of 3,7-disubstituted coumarin derivatives were synthesized. Where treatment of 7-hydroxy-3-substituted coumarins (1a, b) with p-chlorophenacyl bromide afforded (E)-3-acetyl-7-(2-(4-chlorophenyl)-2-hydroxyvinyloxy)-2H-chromen-2-one (2) and ethyl 7-(2-(4-chlorophenyl)-2-oxoethoxy)-2-oxo-2H-chromene-3-carboxylate (3). The acetylation of compounds 2 and 3 with acetic anhydride in diverse conditions yielded acetyl derivatives (4 and 5). 7-hydroxy-2-oxo-N-p-tolyl-2H-chromene-3-carboxamide (6) and 7-(2-(4-chlorophenyl)-2-oxoethoxy)-2-oxo-N-p-tolyl-2H-chromene-3-carboxamide (7) was obtained via condensation of compound 1b or 3 with p-toluidine. Antitumor activities of the synthesized compounds were evaluated on human Hepatocellular cancer cell line (HePG2) and colon carcinoma (HCT-116) cell line. Among the synthesized compounds 2 and 4 have the highest activity against the tested cell lines.

The synthesis of water-soluble heterocyclic compounds was verified on the basis of nonionic surfactants for use as surface-active agents. Surface characteristics such as surface and interfacial tensions, cloud point, wetting time, emulsion stability, foaming height and foaming stability were measured for these surface factors in aqueous solutions. In addition, the critical micelle concentration (CMC), the surface pressure at CMC (πcmc), the effectiveness of surface tension reduction (pC20), the maximum surface concentration (Γma.) and the minimum area/molecule at the aqueous solution/air interface (Amin) were calculated. Moreover, the biodegradability for these nonionic surfactants has been investigated. Furthermore, the antimicrobial evaluation has been evaluated with some surfactants that have demonstrated a potent cytotoxicity as antibacterial, antifungal and anticancer. These surfactants have a good water solubility, low toxicity, environmentally friendly environment, high foam, good emulsifier and easy production that will be used them in various fields such as medical drugs, insecticides, detergents, emulsifiers, cosmetics, inks clothing, leather industry and oil recovery.

A new series of tetra substituted 1,2,4-triazines (4, 5, 7 and 8) was synthesized via the reaction of 3,1-oxazolinone (1) with thiosemicarbazide to give 6-hydroxy-5-(p-hydroxybenzylidene)-3-phenyl-2-(amino) thioxo-1,2,4-triazine (3). Treatment of 1,2,4-triazine derivative 3 with carbon disulphide and p-chlorophenacyl bromide yielded the corresponding 1,2,4-triazine derivatives 4 and 7. Acetylation of tetra-substituted 1,2,4-triazines 4 and 7 with acetic anhydride gave tri acetyl and di acetyl derivatives 5 and 8. Compounds structure was confirmed by IR, H-1, C-13-NMR, MS, and elemental analysis. The cytotoxic activities of some synthesized, 1,2,4-triazines were evaluated on human hepatocellular carcinoma cells (HepG-2) and human colon carcinoma cells (HCT-116) using the MTT method. We found that, compounds 5 (IC50 = 3.60 mu g/mL) and 8 (IC50 = 4.40 mu g/mL) have better activity against HCT-116 cell line than the reference doxorubcin (IC50 = 5.30 mu g/mL), while compound 7 has best activity against HepG-2 cell line.

Indolinone and spiro-indoline derivatives have been employed in the preparation of different important therapeutic compounds required for treatment of anticonvulsants, antibacterial, Antitubercular, and anticancer activities. Schiff bases have been found to possess various pharmacological activities such as antitubercular, plant growth inhibiting, insecticsidal, central nerve system depressant, antibacterial, anticancer, anti-inflammatory, and antimicrobial. Mannich bases have a variety of biological activities such as antibacterial and antifungal activities.

1-(Arylidene)amino-2-thioxo-imidazolidine-4-ones ( 3 a,b) have been synthesized via cyclization of 1-(arylidene)amino-3-(chloroacetyl)thiourease ( 2 a,b) in ethanol in presence of fused sodium acetate under heating. Acetylation of compounds ( 3 a,b) with acetic anhydride yielded the corresponding 1-(arylidene)amino-2-thioxo-3-acetylimidazolidin-4-ones ( 4 a, b). Condensation of compounds ( 3 a,b) with aromatic aldehydes in presence of piperidine yielded the corresponding aryl-[1-(arylidine)amino-2-thioxo-4-oxo-imidazolidin-3-yl)carbanols ( 6 a-d). Halogenation of 1-(phenylethylidene)amino-2-thioxoimidazolidin-4-one ( 3 b) with one mole of bromine produced N-bromo- 2- thioxoimidazolidin-4-one ( 9 ), while brominating 1-(benzylidene)amino-2-thioxoimidazolidin-4-one ( 3 a) with two mole of bromine gave the corresponding 3,5-dibromo-2-thioxoimidazolidin-4-one derivative ( 10 ). The characterization of all synthesized compounds were done by elemental analysis and spectral studies. Moreover, the cytotoxic activities of the synthesized compounds were evaluated against human hepatocellular carcinoma cell line (HePG2) using MTT viability test. The results showed that the investigated compounds have a significantly cytotoxic effect.

A series of novel substituted 6'-(4-chlorophenyl)3,4'-bipyridine-3'-carbonitriles with incorporated pyrazole and/or triazole moieties have been synthesized using 2-(6'-(4-chlorophenyl)-3'-cyano-3,4'-bipyridin-2'-yloxy)acetohydrazide (3) as starting material. Also, the key intermediate 3 reacted with aromatic aldehydes and tosyl chloride to give the corresponding Schiff bases and tosyl hydrazide derivatives, respectively. The antimicrobial of these newly synthesized compounds was evaluated against Bacillus subtilis as Gram-positive bacteria and Trichoderma viride as a fungus; some of these compounds such as 5, 6, 7, 8, 10, 12, and 14 showed excellent activities as antimicrobial agents. Moreover, the cytotoxic activity of the most active compounds was assessed in vitro against human tumor liver cancer cell line (HEPG2); compounds 8, 10, 13a, and 14 showed potent activities relative to Doxorubicin which was used as a reference standard drug in this study.

The 2,3,5- tri substituted –1,2,4triazin -6 - ones (2,3) are synthesized via condensation of 2- phenyl - 4 - (4- Floro benzylidene) 1,3-oxazol -5- one (1) with hydrazine hydrate, semicarbazide, and thiosemicarbazide, followed by cyclization with removal of water molecule. Acetylating compounds 2,3 with acetic anhydride yields the diacetyl derivative 4 and fused triazolo - 1,2,4triazine derivative 5, respectively. Treatment of compound 3a with ethyl chloro acetate in the presence of fused sodium acetate gives the corresponding fused 1,2,4-triazine derivative 6. 3- acetyl- 5,5- di substituted -1,2-dihydro - 1,2,4- triazino-1,2,4-triazin - 1,4,8-triones 7 was prepared via acetylating compound 6 with acetic anhydride under reflux. The structure of the compounds were characterized based on their spectral data. The cyotoxic activities of the prepared compounds have been studied on the tumor cell line human colon carcinoma (HCT- 116) cell using the MTT viability test.

A series of imidazolinone and benzoxazole derivatives (3 and 5) have been synthesized by the condensation of oxazolinone derivatives (2a–c) with aniline and 2-hydroxyaniline. Acetyl derivatives (4, 6 and 7) were prepared via acetylation of compounds 3 and 5 with acetic anhydride and chloroacetyl chloride. The results revealed that imidazolinone and benzoxazole derivatives are potent against the cancer cell lines MCF-7 and HePG2. In particular, benzoxazole derivatives are more potent than imidazolinone derivatives.

A variety of hitherto unknown heterocyclic compounds incorporating the antipyrine moiety are synthesized using 4-acetamidopyrazolone (I) as starting compound.

4-acetamide pyrazolone 2 was synthesized by acetylation of 4-amino antipyrine 1 in excellent yield. 4-acetamide pyrazolone 2 was exploited as a starting material for the syntheses of hitherto unknown different types of new heterocyclic compounds incorporating the antipyrine moiety which expect highly biological activity against various microorganisms. Thus, Claisen condensation of 4-acetamide pyrazolone 2 with diethyl oxalate have been utility to afford new 4-oxaloacetyl antipyrine 3, which upon hydrazinolysis of the ester function to obtain the acetohydrazide derivative 18 which used as starting material to synthesize 1,2,4-triazol 19 and hydrazone 20 derivatives. 4-aminothiophene carboxylate derivatives 6, 7 were synthesized by utility of Gewald reaction. On the other hand, Michael type addition of the enolate ion of acetyl functions in acetamide pyrazolone 2 to the activated double bond in arylidenemalonoester to furnish pyrane derivative 9 was done. Finally, 4-acetamide pyrazolone 2 was treated with aromatic substituted aldehyde to exhibit thiophenacrylamide derivative 10. Compound 6 gave characteristic reaction for enaminonitriles, thus, the behavior of o-aminoester of 4-aminothiophene carboxylate derivative 6 toward electrophilic reagent, one carbon donars, amide and acid was also investigated to afford the correspondence thiophene derivatives 11,12,13,15 and 16. In addition, treatment of carboxamide derivative 16 with thionyl chloride afforded the thienothiadiazine derivative 17. The characterization of all synthesized compounds was done by elemental analysis and spectral studies. Moreover, all the synthesized compounds were tested against antimicrobial activities by the disc diffusion method, which exhibited higher promising biological activities.