An efficient protocol for the synthesis of novel fused N-heteropolycycles 10a-f (tetracyclic-fused and bridged dibenzo-azepinone,-azocinones,-azoninone, benzo [b] pyrido [3, 2-f] azocinone and benzo [c] pyrido [3, 2-g] azoninones) via combined Darzens and Friedel-Crafts methodologies is described. The starting ketones 5a, b were conveniently obtained via cyanoethylation of aminoxylenes 1a, b followed by hydrolysis of the resulting nitriles 3a, b to the corresponding carboxylic acids 4a, b and were finally acylated by intramolecular Friedel-Crafts reaction. The key acetylated intermediates 7a, b were obtained by Darzens condensation. Subsequently, two steps led to substituted heterocyclic acids 9a-f which successfully underwent Friedel–Crafts cycloacylations mediated by AlCl3/CH3NO2, TfOH or P2O5 catalysts. The method offers readily access to diverse drug-like 10a-f scaffolds in moderate to good yields. a: n= 0, x= 0, Y= CH; b: n= 0, x= 1, Y= CH; c: n= 0, x= 1, Y= N; d: n= 1, x= 0, Y= CH; e: n= 1, x= 1, Y= CH; f: n= 1, x= 1, Y= N

The inhibitory characteristics of two recently synthesized biosurfactants based on amino acids, namely sodium Nhexadecyl glycine (I) and sodium N-hexadecyl valine (II), concerning copper corrosion in 1.0 M HNO3 were studied at variance of temperatures. FTIR analysis was utilized to identify the chemical structures of both synthesized biosurfactants. Various techniques were employed in this study. According to the results, the synthesized biosurfactants were played as proficient inhibitors for copper corrosion and their inhibition efficiencies (% IEs) were concentration- and structure-dependent with respect to them. At a concentration of 400 mg/L of the synthesized biosurfactants and at 298 K, the average% IE was found to be 90% for biosurfactant I and 85% for biosurfactant II. The gained higher% IEs were suggested to as a result of the potent adsorption of these biosurfactants on the surface of copper and the type of adsorption was discovered to be physical and followed Langmuir adsorption isotherm. The obtained findings signified that the synthesized biosurfactants exhibited mixed-type and interface-type inhibitors. The thermodynamic and kinetic parameters were assessed and discussed. Furthermore, the kinetics of corrosion of copper as well as its inhibition were also investigated. The density functional theory (DFT) and molecular dynamics (MD) simulations emphasized the inhibitory mechanism of the examined biosurfactants and proved the adsorption of the biosurfactants’ molecules on the copper surface. Theoretical modeling also demonstrated that the biosurfactant I exhibited a greater% IE compared to biosurfactant II. The experimental results gained from all employed measurements are largely reliable with each others and are in a good consistent with the theoretical studies signifying the validity of these results.

Although carbon steel (CS) is an essential component utilized in many industries, it regrettably corrodes when exposed to acidic conditions. Schiff bases have recently become more concerned with the corrosion prevention of CS. Hydrazides and the related compounds shown to be effective inhibitors of CS corrosion in acids. These compounds are commonly employed as origins or intermediates to several key molecules in the synthesis of organic compounds, and they are highly sought after due to their wide range of biological and therapeutic applications. They have anti-bacterial, anti-malarial, anti-fungal, and anticancer properties, as well as corrosion protection. Hence, the inhibitory effectiveness of a new synthesized (E)-N’-(thiophen-2-ylmethylene) isonicotinohydrazide (TMNH) Schiff-base for the corrosion of CS in 1 M HCl was explored. The structure of TMNH was validated by FT-IR and 1 H NMR spectroscopy. A number of chemical, spectral, and electrochemical techniques such as potentiodynamic polarization (PDP), electrochemical impedance spectroscopy (EIS), and mass loss (ML) have been used to evaluate its anticorrosion power. PDP measurements showed that it is a mixed-type inhibitor. In addition, EIS measurements showed that Rct increased sharply from 37 without the corrosion inhibitor to 589 Ω cm-2 in the presence of 1 mM TMNH and from PDP scans, the corresponding icorr decreased dramatically from 0.6158 to 0.0314 μA cm-2. ML tests have proven their effectiveness, achieving an inhibitory efficiency of 95.3 %. Adsorption studies were also conducted to determine the nature of the corrosion retardation mechanism. The TMNH inhibitor was spontaneously chemically/physically adsorbed onto the CS surface following the Langmuir isotherm. Statistical calculations were also applied to verify the accuracy of the experimental results. The Monte Carlo model showed that the inhibitory molecules adsorbed flat on only one side, increasing the chances of adsorption

Background

Several studies have been reported previously on the bioactivities of different extracts of marine molluscs. Therefore, we decided to evaluate the cytotoxic and antimicrobial activities of S. pharaonis ink as a highly populated species in the Red Sea. We extracted the flavonoids from the ink and analyzed their composition. Then we evaluated systematically the cytotoxic and antimicrobial properties of this extract. A pharmacokinetic study was also conducted using SwissADME to assess the potential of the identified flavonoids and phenolic compounds from the ink extract to be orally active drug candidates.

Results

Cytotoxic activity was evaluated against 5 cell lines (MCF7, Hep G2, A549, and Caco2) at different concentrations (0.4 µg/mL, 1.6 µg/mL, 6.3 µg/mL, 25 µg/mL, 100 µg/mL). The viability of examined cells was reduced by the extract in a concentration-dependent manner. The highest cytotoxic effect of the extract was recorded against A549 and Hep G2 cancer cell lines cells with IC_{50 =} 2.873 and 7.1 µg/mL respectively. The mechanistic analysis by flow cytometry of this extract on cell cycle progression and apoptosis induction indicated that the extract arrests the cell cycle at the S phase in Hep G2 and MCF7, while in A549 cell arrest was recorded at G1 phase. However, it causes G1 and S phase arrest in Caco2 cancer cell line. Our data showed that the extract has significant antimicrobial activity against all tested human microbial pathogens. However, the best inhibitory effect was observed against Candida albicans ATCC 10,221 with a minimum inhibitory concentration (MIC) of 1.95 µg/mL. Pharmacokinetic analysis using SwissADME showed that most flavonoids and phenolics compounds have high drug similarity as they satisfy Lipinski’s criteria and have WLOGP values below 5.88 and TPSA below 131.6 Ų.

Conclusion

S. pharaonis ink ethanolic extract showed a promising cytotoxic potency against various cell lines and a remarkable antimicrobial action against different pathogenic microbial strains. S. pharaonis ink is a novel source of important flavonoids that could be used in the future in different applications as a naturally safe and feasible alternative of synthetic drugs.

Self-assembly of benzene-1,4-dicarboxylate with Cu (II) using ultrasonic assisted approaches with 2-aminothiazole as secondary ligand produce a coordination polymer of the formula {[Cu (BDC)(AZ) (H₂O)]. H₂O}_n. The structure was investigated using elemental analysis, IR spectroscopy, X-ray diffraction (XRD) and Transmission electron microscopy (TEM). A crystalline coordination polymer was obtained via the ultrasonic irradiation. Copper compounds exhibited promising inhibitory action against six human pathogenic bacteria (Bacillus subtilis, Bacillus cereus, Escherichia coli, Klebsiella pneumoniae, Micrococcus luteus, and Serratia marcescens). The most effective antibacterial treatments were after sonication for 70 min especially at 100 µg/ml gives total counts 32.96 × 10⁷ ± 0.56, 32.68 × 10⁷ ± 0.84, 28.32 × 10⁷ ± 1.2, 9.16 × 10⁷ ± 0.52, 20.92 × 10⁷ ± 0.2, and 30.36 × 10⁷ ± 0.28, for B. subtilis, B. cereus, E. coli, K. pneumoniae, M. luteus, and S. marcescens comparing with control samples 82.84 × 10⁷ ± 5.96, 94.04 × 10⁷ ± 3, 65.24 × 10⁷ ± 1.08, 32.92 × 10⁷ ± 0.6, 36.92 × 10⁷ ± 0.2, and 59.52 × 10⁷ ± 0.4, respectively.

5-Acetyl-3-cyano-6-methyl-4-styryl/(4-methxphenyl)pyridine-2(1H)-thiones (IIa), (IIb) were synthesized via reacting ylidenecyanothioacetamides (Ia), (Ib) with acetylacetone. Treatment of compound (IIa) with certain N-aryl-2-chloroacetamides, under mild basic conditions (sodium acetate trihydrate), gave the expected 2-((5-acetyl-3-cyano-6-methyl-4-styrylpyridin-2-yl)thio)- N-arylacetamides (IIIa–IIIf). Conversion of (IIIa–IIIf) into the corresponding thienopyridines (IVa–IVf) was carrired out in boiling ethanol containing anhydrous sodium carbonate. Reaction of (IVb),(IVf) with 2,5-dimethoxytetrahydrofuran afforded pyrrolylthienopyridines (Vb), (Vf). Cyclocondensation of (IVb), (IVf) with triethyl orthoformate produced pyridiothienopyrimidinones (VIb), (VIf). Diazotization of compounds (IVb–IVd) afforded triazinones (VIIb–VIId). Compound (IIa) was treated with 2-chloromethyl-1H-benzimidazole to afford 2-(((1H-benz[d]imidazol-2-yl)methyl)thio)-5-acetyl-4-(4-methoxy- yphenyl)-6-methylnicotinonitrile (VIII). Cyclization of (VIII) into 1-(3-amino-2-(1H-benz[d]imidazol- 2-yl)thienopyridine (IX) was carried out. Compound (IX) underwent different reactions with some reagents to furnish condensed benzimidazoles (X–XIII). [1,2,3]Triazine (XIV) was synthesized via diazotization of (IX). Some of our target derivatives had been examined in vitro for their antibacterial activities against MRSA and E. coli, and promising results obtained. Most of new styrylpyridines were evaluated for their insecticidal activity towards A. gossypii (Glover, 1887) and considerable results recorded.

2-((3-cyano-4,6-distyrylpyridin-2-yl)thio)acetophenone (2) was synthesized by the reaction of 3-cyano-4,6-
distyrylpyridin-2(1H)-thione (1) with an alkylating agent, phenacyl bromide in the presence of fused sodium
acetate and ethanol. Compound 2 underwent Thorpe-Ziegler cyclization upon heating in ethanolic sodium
ethoxide solution to yield the target, 3-amino-2-benzoyl-4,6-distyrylthieno[2,3-b]pyridine (3). Elemental and
spectral characterizations of the newly synthesized compounds 2 and 3 have been achieved. Both compounds 2 and 3 exhibited significant insecticidal activities after treated for 24 and 48 h compared with the reference compound, acetamiprid, when screened for their insecticidal activity against the nymphs and adults of cowpea aphid, Aphis craccivora Koch. Therefore, the results obtained are very promising,and accentuate on the importance of such heterocyclic pyridine compounds as efficient pesticides.

Ethyl 5-cyano-1,6-dihydro-2-methyl-4-(2′-thienyl)-6-thioxonicotinate (A) was synthesized and reacted with ethyl chloroacetate in the presence of sodium acetate or sodium carbonate to give ethyl 5-cyano-6-((2-ethoxy-2-oxoethyl)thio)-2-methyl-4-(2′-thienyl)nicotinate (1a) or its isomeric thieno[2,3-b]pyridine 2a. 3-Aminothieno[2,3-b]pyridine-2-carboxamide 2b was also synthesized by the reaction of A with 2-chloroacetamide. The reaction of 1a with hydrazine hydrate in boiling ethanol gave acethydrazide 3. Heating ester 1a with hydrazine hydrate under neat conditions afforded 3-amino-1H-pyrazolo[3,4-b]pyridine 10. Compounds 2b, 3, and 10 were used as precursors for synthesizing other new thieno[2,3-b]pyridines and pyrazolo[3,4-b]pyridines containing mainly the ethyl nicotinate scaffold. Structures of all new compounds were confirmed by elemental and spectral analyses. Most of the obtained compounds were evaluated for their insecticidal activity toward the nymphs and adults of Aphis gossypii (Glover,1887). Some compounds such as 4, 9b, and 9c showed promising results. The effect of some sublethal concentrations, less than LC₅₀, of compounds 4, 9b, and 9c on the examined Aphis was subjected to a further study. The results demonstrated that exposure of A. gossypii nymphs to sublethal concentrations of compounds 4, 9b, and 9c had noticeable effects on their biological parameters, i.e., nymphal instar duration, generation time, and adult longevity. The highest concentration C1 of all three compounds increased the nymphal instar duration and generation time and decreased adult longevity and vice versa.

This work reports the preparation of a new dihydroisoquinoline derivative whose structure was characterized by IR, NMR (¹H, ¹³C), MS and verified through single-crystal X-ray analysis. The mean planes of the acetyl and 4-chlorophenyl groups in the title molecule are nearly perpendicular to that of the pyridine ring. In the crystal, π-stacking and C—H···O hydrogen bond interactions involving the pyridine ring and the nitrile group of an adjacent molecule form the full 3-D structure. Hirshfeld surface (HS) analysis shows the topology of the molecules in the crystal packing. Fingerprint (FP) diagrams show the percentage contribution of several intermolecular interactions where H‧‧‧H interactions have a significant contribution (46%). The DFT study reveals a low HOMO-LUMO gap and significant charge transfer is indicated by the natural bonding orbitals (NBO) and frontier molecular orbital (FMO) analyses. Non-covalent interactions and bond characteristics were investigated using the quantum theory of atom in the molecule (QTAIM) and ELF analysis. FMO analysis was used to calculate the HOMO-LUMO energy gap and orbital energies. Using the DFT method, parameters such as global reactivity were calculated. Using the implicit solvent model, properties such as optical and nonlinear optical (NLO) were characterized in the solvent (water) phase and gas phase. The affinity of the title molecule for Monoamine Oxidase B was examined using molecular docking and molecular dynamics studies and these results showed good binding of the target molecule.