Synthesis and antimicrobial activity of fused isatin and diazepine derivatives derived from 2-acetyl benzofuran

Acetyl benzofurans 1a, 1b reacted with isatins 2a–2f in the presence of pyridine to give corresponding 3-[2-(1-benzofuran-2-yl)-2-oxoethyl]-3-hydroxy-1,3-dihydro-2H-indol-2-one derivatives 3a–3l. Dehydration of the latter in acidic media led to the corresponding α,β-unsaturated ketones 4a–4l. The structures of newly synthesized compounds 3a–3l and 4a–4l were established on the basis of analytical and spectral data. The synthesized compounds were screened for their antibacterial and antifungal activities. Compounds 5d, 5f, and 5h displayed excellent antimicrobial activity. The synthesized compounds were studied for docking on the enzyme, Glucosamine-6-phosphate Synthase.     

Phosphorus–nitrogen compounds part 33: in vitro cytotoxic and antimicrobial activities,DNA interactions,syntheses, and structural investigations of new mono(4-nitrobenzyl)spirocyclotriphosphazenes

The condensation reactions of hexachlorocyclotriphosphazene, N₃P₃Cl₆, with N-alkyl-N′-mono(4-nitrobenzyl)diamines (1–3), NO₂PhCH₂NH(CH₂) _n NHR₁ (R₁ = CH₃ or C₂H₅), led to the formation of the mono(4-nitrobenzyl)spirocyclotriphosphazenes (4–6). The tetra-pyrrolidino (4a–6a), piperidino (4b–6b), and 1,4-dioxa-8-azaspiro[4,5]decaphosphazenes (4c–6c) were prepared from(for) the reactions of partly substituted compounds (4, 5, and 6) with excess pyrrolidine, piperidine, and 1,4-dioxa-8-azaspiro[4,5]decane (DASD), respectively. The partly substituted geminal (4d and 5d) and cis-morpholino (6d) phosphazenes were isolated from the reactions of excess morpholine in boiling THF and o-xylene, but the expected fully substituted compounds were not obtained. The structures of all the phosphazene derivatives were determined by elemental analyses, MS, FTIR, ¹H, ¹³C{¹H}, ³¹P{¹H} NMR, HSQC, and HMBC techniques. The crystal structures of 4, 6, 4a, and 5a were verified by X-ray diffraction analysis. In addition, in vitro cytotoxic activities of fully substituted phosphazenes (4a–6c) against HeLa cervical cancer cell lines (ATCC CCL-2) and the compounds 4a and 4c against breast cancer cell lines (MDA-MB-231) and L929 fibroblast cells were evaluated, respectively. Apoptosis effect was determined by MDA-MB-231 cancer cell lines and fibroblast cells. The MIC values of the compounds were in the ranges of 9.8–19.5 µM. The compounds 6, 5a, 6a, 5b, and 6d have greater MIC activity against bacterial and yeast strain. The investigation of DNA binding with the phosphazenes was studied using plasmid DNA. The phosphazene derivatives inhibit the restriction endonuclease cleavage of plasmid DNA by BamHI and HindIII enzymes. BamHI and HindIII digestion results demonstrate that the compounds bind with G/G and A/A nucleotides.     

One-pot multicomponent synthesis of novel 1-thiazolyl-5-coumarin-3-yl-pyrazole derivatives and evaluation of their cytotoxic activity

A series of novel 1-thiazolyl-5-coumarin-3-yl-pyrazole derivatives (4a–l) were synthesized via one-pot multicomponent reaction of 5-substituted salicylaldehydes (1a–c), 4-hydroxy-6-methyl-2H-pyran-2-one (2) and 2-hydrazinyl-4-arylthiazoles (3a–d) in acetonitrile using a catalytic amount of piperidine under reflux conditions. This multicomponent approach has advantages such as reduced reaction time and a high product yield percentage when compared with corresponding multistep approaches. All the synthesized compounds were evaluated for their cytotoxic activity against Hep G2 (hepatocellular liver carcinoma) and MCF-7 (breast cancer) cell lines and compared with the standard drug Doxorubicin. Among all the compounds, compounds 4d against Hep G2, 4k against MCF-7 and 4e against both Hep G2 & MCF-7 showed excellent cytotoxic activity.     

Synthesis of hydrazone derivatives of benzofuran and their antibacterial and antifungal activity

A series of benzofuran hydrazones 6a–6n were synthesized from benzofuran aldehyde and substituted aromatic hydrazides 5a–5n. Structures of all compounds were confimed by IR, ¹H and ¹³C NMR, and Mass spectral data. These compounds were evaluated for their antibacterial activity against gram-negative bacteria (Escherichia coli, –ve), gram-positive bacteria (Bacillus Subtillis, +ve), and antifungal activity against Candida albicans. All compounds demonstrated considerable activity against bacteria and fungi.     

Synthesis and antioxidant evaluation of some new 2-benzoylamino-5-hetaryl-1,3,4-oxadiazoles

A series of new functionalized 2-benzoylamino-5-hetaryl-1,3,4-oxadiazoles were efficiently synthesized via the reaction of the versatile key intermediates, 2-benzoylamino-5-cyanomethyl-1,3,4-oxadiazole (1) and N-(5-(5-amino-3-phenylamino)-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)-benzamide (13), with some appropriate electrophilic reagents. The structures of the newly synthesized compounds were established on the basis of elemental analyses, spectral data, and by alternative synthesis wherever possible. The mechanisms of the studied reactions are discussed. Also, we evaluate the antioxidant activity of some representative examples of the newly prepared compounds. Among the synthesized compounds, 2-benzoylamino-5-cyanomethyl-1,3,4-oxadiazole (1) and N-(5-(7-methyl-5-oxo-2-(phenylamino)-4,5-dihydropyrazolo[1,5-a]pyrimidin-3-yl)-1,3,4-oxadiazol-2-yl)benzamide (17) showed excellent antioxidant activity and exhibited high protection against DNA damage induced by the Bleomycin iron complex.     

Synthesis and properties of novel stilbene-twelve alkyl quaternary ammonium salts as antibacterial optical whitening agents

Four novel stilbene-twelve alkyl quaternary ammonium salts 5a–d were synthesized. All synthesized compounds were characterized by FT-IR, ¹H-NMR and elemental analysis. Compounds 5a–d showed efficient whitening effect on cotton fiber and high fastness. Furthermore, compound 5c showed better stability to light than C186 in aqueous solution. The preliminary biological experiment demonstrated compounds 5a–d possessed significant antibacterial activities. Among them, compound 5d turned out to be the most active compound against Candida albicans with MIC₅₀ 4 μg/mL as well as E. coli with MIC₅₀ 16 μg/mL.     

Green synthesis and antibacterial evaluation of some new 1-aryl-3-(1-aryl-1<Emphasis Type="Italic">H</Emphasis>-[1,2,3]triazol-4-yl)-propenones

A new series of 1-aryl-3-(1-aryl-1H-[1,2,3]triazol-4-yl)propenones (6a–6j) was synthesized by condensation of substituted acetophenones (5a–5c) with substituted 1-aryl-1H-[1,2,3]triazole-4-carbaldehydes (4a–4d) in the presence of potassium hydroxide under conditions of grinding and microwave irradiation. All the newly synthesized compounds were characterized by the IR, NMR, and mass spectroscopic analyses and their antibacterial activity against gram-positive and gram-negative bacterial strains was evaluated. Among the compounds synthesized, better activity was exhibited by 6a, 6c, 6f, 6g, and 6i.     

Synthesis and in vitro cytotoxic evaluation of some novel hexahydroquinoline derivatives containing benzofuran moiety

A series of new ethyl 4-(2-(benzofuran-2-yl)-4-substituted-1,4,5,6,7,8-hexahydroquinolin-1-yl)-benzoate 3a–c was synthesized by Michael condensation of benzofuran chalcones 1a–c and cyclohexanone to give 2-(2-benzofuranyl)-4-substituted-5,6,7,8-tetrahydro-4-H -chromene 2a–c, followed by reaction of the latter with ethyl 4-aminobenzoate. Condensation of 3a–c with different amines afforded the corresponding amides 4a–e. On the other hand, upon treatment compounds 3a–c with hydrazine hydrate gave the benzohydrazide derivatives 5a–c. The reaction of compounds 5a–c with different thio/isocyanate gave the corresponding thiosemicarbazide and semicarbazide derivatives 6a–c. Meanwhile compounds 5a–c were reacted with ethyl cyanoacetate and different β-dicarbonyl compounds such as acetyl acetone, ethyl acetoacetate, and diethyl malonate to afford pyrazolyl derivatives 7a, b; 8a, b; 9a, b; and 10a–c, respectively. Moreover, 5a–c were reacted with carbon disulfide to synthesize the corresponding oxadiazolyl derivatives 11a–c, while their condensation with different aromatic aldehydes gave the corresponding Schiff bases 12a–d. Cytotoxic evaluation of some of the newly synthesized compounds against human hepatocellular carcinoma cell lines (HepG-2) revealed that the tested compounds produce promising inhibitory effect against the growth of HepG-2 cells with IC₅₀ values ranged from 11.9 to 19.3 µg/mL.     

Heterospin biradicals based on new piperidineoxyl-substituted 3,6-di-<Emphasis Type="Italic">tert</Emphasis>-butyl-<Emphasis Type="Italic">o</Emphasis>-benzoquinone

A nucleophilic addition reaction of 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (OH-TEMPO) to 3,6-di-tert-butyl-o-benzoquinone was used to obtain a new sterically hindered o-benzoquinone (1) containing 2,2,6,6-tetramethylpiperidineoxyl functional group, which was characterized by IR spectroscopy, mass spectrometry, elemental analysis, and X-ray diffraction. A one-electron reduction of 1 with potassium and thallium is an efficient method for the generation of earlier unknown heterospin biradicals 5a and 5b, respectively, containing nitroxide and o-semiquinone radical centers. Analysis of the hyperfine structure of the ESR spectra of biradicals 5a and 5b in solution showed that they belong to the group of heterospin biradicals with strong (J >> a) and fast exchange interaction between the radical centers.     

Synthesis and crystal structures of (2.2.2-cryptand)rubidium chloride and bromide hydrates

Two complexes, (2.2.2-cryptand)rubidium chloride and bromide hydrates [Rb(Crypt-222]Hal · 3.5H₂O (Hal = Cl (I) and Br (II)), are synthesized. The structures of isomorphic crystals of compounds I and II are studied by X-ray diffraction analysis. The crystals are trigonal: space group P \(\overline 3 \), Z = 2; I: a = 11.810 Å, c = 11.302 Å; II: a = 11.890 Å, c = 11.402 Å. The structures are solved by a direct method and refined by the full-matrix least-squares method in the anisotropic approximation to R = 0.060 (I) and 0.077 (II) for 2650 (I) and 2700 (II) independent reflections (CAD-4 automated diffractometer, λMoK _α radiation). In crystals of complexes I and II, the [Rb(Crypt-222)]⁺ cation of the host-guest type lies on the crystallographic axis 3 and has the approximate symmetry D ₃. In complexes I and II, the coordination polyhedron of the Rb⁺ cation is a two-base-centered trigonal prism somewhat distorted to an antiprism. The crystals of compounds I and II contain H-bonded disordered cubes of the water molecules and Cl^? or Br^? anions.     

Synthesis,antibacterial activity,and fluorescence properties of a novel series from [2,4-dioxochromen-3(4<Emphasis Type="Italic">H</Emphasis>)methyl]amino acid

A new solvent-free method for synthesis of starting compounds 2,4-dioxochromen-3(4H)methyl amino acetic acid derivatives 1a–e via a green approach is reported. Also, the behavior of compound 1a towards various nitrogen nucleophiles such as primary amines, hydrazine hydrate, and hydroxylamine hydrochloride to give corresponding compounds 2–4 was studied. Furthermore, chlorination of compound 1a using a mixture of PCl₅/POCl₃ to yield acid chloride derivative 5 and the reaction of the latter compound 5 with various amino acids to obtain dipeptide compounds 6a–e are described. Moreover, cyclization of compound 1a in alkaline medium to afford dihydrochromeno[3,4-c]pyrrole-1-carboxylic acid 7 and cyclization of 6b in acidic medium, namely Ac₂O, to yield piperazine derivative 8 are reported. Also, reaction of compound 1a with maleic anhydride in dioxane to afford Diels–Alder adduct 9, which posteriorly reacted with hydrazine hydrate to give 10, was investigated. Most of the newly synthesized compounds were screened against Gram-positive and Gram-negative bacteria, with compound 5 exhibiting the maximum inhibition zone towards all four types of bacteria. In addition, the absorption and fluorescence emission of some of the substituted coumarins were studied in dioxane, revealing that the substituents altered both the absorption and fluorescence emission maxima.     

Synthesis and crystal structures of binuclear complexes of cobalt(II) and cadmium(II) diisobutyldithiophosphinates with hexamethylenetetramine

Heteroligand complexes [Co₂(HMTA)(iso-Bu₂PS₂)₄] (I) (μ_eff = 4.67 μB) and [Cd₂(HMTA)(iso-Bu₂PS₂)₄] (II) have been synthesized. Single crystals of compounds I and II have been obtained. The crystals are monoclinic: a = 32.622(2) Å, b = 9.4891(6) Å, c = 21.7570(13) Å, β = 125.774(1)^o, V = 5464.3(6) Å,³, Z = 4, ρ_calcd = 1.331 g/cm³ for I; a = 34.6092(7) Å, b = 9.5595(2) Å, c = 22.3473(5) Å, β = 127.144(1)^o, V = 5893.5(2) Å, Z = 4, ρ_calcd = 1.355 g/cm³ for II; space group for both complexes C2/c. Structures I and II are based on discrete binuclear molecules. The coordination polyhedra of the Co and Cd atoms are distorted tetragonal pyramids NS₄, with the bases formed by four S atoms of two bidentate chelating ligand iso-Bu₂PS ₂ ^? and the axial vertices occupied by N atoms of bidentate bridging HMTA ligand. The character of interaction of the molecules in structures I and II is considered.     

Syntheses,crystal structures and in vitro anticancer activities of oxovanadium(IV) complexes of amino acid Schiff base and 1,10-phenanthroline ligands

Four oxovanadium(IV) complexes, namely [VO(desa-met)(phen)]·MeOH·2H₂O (1) (desa-met = Schiff base derived from 4-(diethylamino)salicylaldehyde and dl-methionine, phen = 1,10-phenanthroline), [VO(o-van-met) (phen)]·MeOH·CH₂Cl₂·3H₂O (2) (o-van-met = Schiff base derived from o-vanillin and dl-methionine), [VO(dtbs-napa)(phen)]·2H₂O (3) (dtbs-napa = Schiff base derived from 3,5-di-tert-butyl salicylaldehyde and 3-(1-naphthyl)-l-alanine) and [VO(hyna-napa)(phen)]·1.5H₂O (4) (hyna-napa = Schiff base derived from 2-hydroxy-1-naphthaldehyde and 3-(1-naphthyl)-l-alanine), were synthesized and characterized by IR, HRMS, UV–vis spectra, molar conductance and single-crystal X-ray diffraction (XRD). X-ray structural analysis showed that the V(IV) atoms in all four complexes are six-coordinated in a distorted octahedral environment. In the crystals of complexes 1 and 2, π–π stacking interactions together with hydrogen bonds connect the molecular units into 2D networks. Meanwhile, CH–π stacking interactions are observed between the aromatic rings in the crystals of 1 and 4, while the π–π stacking interactions between aromatic rings in the crystals of 2 and 3 are arranged with a face-to-face mode. The in vitro anticancer activities of these complexes against A-549 and HeGp2 cells were tested by MTT assay.     

Synthesis,antifungal and insecticidal activity of novel [1,2,4]triazolo[4,3-<Emphasis Type="Italic">a</Emphasis>]pyridine derivatives containing a sulfide substructure

A series of [1,2,4]triazolo[4,3-a]pyridine derivatives bearing a sulfide substructure was designed, synthesized and characterized via ¹H·NMR, ¹³C·NMR, IR and elemental analyses. Bioassay Results indicated some of the derivatives displayed good fungicidal activity on Rhizoctonia cerealis, moderated insecticidal activity against Plutella xylostella and good insecticidal activity on Helicoverpa armigera. The inhibitory effects of compounds 4g and 4u against Rhizotonia cerealis were 70.9% at 50 μg mL^?1; the IC₅₀ values of compounds 4d and 4s against Plutella xylostella were 43.87 and 50.75 μg mL^?1, respectively. And the IC₅₀ values of compounds 4d, 4q, and 4s on Helicoverpa armigera were 58.3, 77.14 and 65.31 μg mL^?1, respectively, which were better than that of commercial chlorpyrifos (103.77 μg mL^?1).     

Facile synthesis of some condensed 1,3-thiazines and thiazoles under conventional conditions: antitumor activity

1,3-Thiazine 3 was obtained from cinnamoyl thiourea derivative 2 as the kinetic control product. Refluxing of 2 with sodium ethoxide afforded pyrimidine derivative 4. Moreover, stirring of 2 with bromine/acetic acid gave thiazole 5 that was condensed with o-phenylene diamine forming benzimidazole 6. Heating of arylthiourea 8 with maleic anhydride or phenacyl chloride afforded thiazole derivatives 9 and 10, respectively. Condensation of compound 10 with o-phenylene diamine gave benzimidazole 11. Reaction of p-amino benzoic acid with chloro acetyl isothiocyanate, acetylacetone and ethylacetoacetate produced imidazole 14, enaminone 15 and crotonate 16 derivatives, respectively. Stirring a mixture of benzoyl isothiocyanate with 15 and/or 16 resulted in pyridine-2-thione 17. The yields of the prepared compounds were 41–93%. The experimental section is simple and easy. The detailed synthesis, spectroscopic data, IC₅₀ and antitumor activity of the synthesized compounds were reported. The cytotoxicity of the newly synthesized products showed that compound 4 is the most active compound towards the cancer cell line at which its reactivity is higher than that of the standard doxorubicin (anticancer reference drug).     

Synthesis of novel coumarin substituted amide derivatives and their antibacterial activities

A series of novel coumarin substituted amide derivatives were synthesized and evaluated for their antibacterial activities. Result indicated that compounds 3f, 3g, 3h, 3i, 3j, 3k, 3l, 3m, 3n, 3o and 3q exhibited excellent antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas citri subsp. Citri (Xcc) in vitro, which were better than those of commercial agricultural antibacterial thiodiazole-copper. The title compounds with electron-withdrawing group showed better antibacterial activities than those of compounds with electron-donating group, and the title compounds bearing the same substituent group exhibited better antibacterial activities against Xcc than antibacterial activities against Xoo.     

Hyperconjugative interactions are the main responsible for the anomeric effect: a direct relationship between the hyperconjugative anomeric effect,global hardness and zero-point energy

The correlations between the global hardness (η), hyperconjugative anomeric effect, Pauli exchange-type repulsions, electrostatic model associated with dipole–dipole interaction and structural parameters in 2-fluorotetrahydropyran, -thiopyran, -selenopyran (1–3) and their chloro- (4–6) and bromo-analogs (7–9) were investigated by means of the conventional and range-corrected functionals and natural bond orbital (NBO) interpretation. By deletion of the HC-exo-AE and HC-endo-AE, the equatorial conformations of compounds 1–9 become more stable than their corresponding axial forms, revealing that anomeric relationships in compounds 1–9 have the hyperconjugative anomeric effect origins while the electrostatic model associated with dipole–dipole interaction does not play a determining role on the variations of the anomeric relationships in these compounds. The anomeric relationships in compounds 1–3 have no Pauli exchange-type repulsions origin, but it has a significant impact on the conformational preferences in compounds 4–6 and 7–9. A canonical molecular orbital interpretation was conducted to investigate the correlations between the linear combinations of natural bond orbitals in the HOMOs, LUMOs and the global hardness (η) values. There is a direct relationship between the hyperconjugative anomeric effect, global hardness (η) and zero-point energies in compounds 1–3, 4–6 and 7–9. The harder axial conformations with the greater hyperconjugative anomeric effect and zero-point energy values are more stable than their corresponding equatorial forms.     

Synthesis and in vitro anticancer,antibacterial, and antioxidant studies of unsymmetrical Schiff base derivatives of 4-[(1<Emphasis Type="Italic">E</Emphasis>)-<Emphasis Type="Italic">N</Emphasis>-(2-aminoethyl)ethanimidoyl]benzene-1,3-diol

Schiff bases such as 2-hydroxy-1-(4-hydroxyphenyl)ethanone (DHAP) and its derivatives have attracted attention because they are useful in design and development of novel organic compounds for potential pharmaceutical applications. In this work, a series of 4-[(1E)-N-(2-aminoethyl)ethanimidoyl]benzene-1,3-diol (4a–h) Schiff bases were synthesized by reaction of ethylenediamine, DHAP, and appropriate aldehyde moieties. The compositions of the prepared compounds were established using elemental analysis and Fourier-transform infrared (FTIR) and ultraviolet–visible (UV–Vis) spectroscopies. The compounds were screened against three Gram-positive and three Gram-negative bacteria, and the results compared with standard drugs ciprofloxacin and amoxicillin. Compounds 4g, 4h were found to have higher activity against Staphylococcus aureus with minimum inhibitory concentration (MIC) value of 2.5 mg/mL, while compounds 4f and 4h inhibited Escherichia coli with MIC values of 2.5 and 5 mg/mL, respectively. The IC₅₀ values of compounds 4a–h for scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical ranged from 2.63 ± 0.79 to 3.85 ± 0.83 µM with good correlation coefficient of R ² = 0.957–0.994. In vitro anticancer screening of the compounds showed that compounds 4f, 4h, and parthenolide efficiently affected cell viability of cancer cell line MCF-7 with IC₅₀ values of 4.10 ± 1.32, 4.01 ± 2.26, and 0.44 ± 2.02 µM, respectively.     

Synthesis,crystal structures,and characterization of a new substituted 1,2,4-triazole and its two Co(II)/Mn(II) complexes

A new triazole-substituted ligand H₂L (H₂Trza = 3-amino-1H-1,2,4-triazole-5-acetate) and its two new isomorphic compounds [M(HTrza)₂(_H2O)₂] ? 2H₂O (Co(I) and Mn(II)) have been synthesized and characterized structurally. Their X-ray crystal structures (CIF files CCDC nos. 906893 for I and 906892 for II) show that H₂L belongs to a tetragonal system; space group P4₃ with a = b = 5.0445(13), c = 27.054(10) Å; Z = 4. Complex I belongs to a monoclinic system; space group P2₁/n with a = 7.6543(8), b = 7.3453(8), c = 13.6283(14) Å; β = 91.5990(10)°, Z = 2. Complex II belongs to a triclinic system; space group with a = 6.8550(15), b = 8.0630(18), c = 15.173(4) Å; α = 84.794(4)°, β = 79.005(3)°, γ = 73.779(4)°, Z = 2. X-ray analysis demonstrates that compound H₂L is found to contain a H₂Trza and a lattic water molecule; complexes I and II are discrete mononuclear species. The central Co(II) and Mn(II) atoms exhibit octahedral coordinations, type 4 + 2. In two compounds, the coordination entities are further organized via hydrogenbonding interactions to generate uniform supramolecular networks. Thermal stabilities of two compounds were examined by thermogravimetric analysis.     

Molecular structure investigation and biological evaluation of Michael adducts derived from dimedone

Trimolecular salt Michael adducts 2a–c were synthesized in excellent yields up to 92 % via one-pot multicomponent reactions in an aqueous medium. The chemical structures of compounds 2a–c were characterized by X-ray single-crystal diffraction techniques. Calculations of the density functional theory for the synthesized compound were performed. The stability of the products was deduced by TGA analysis. Compounds 2a–c were screened in vitro for different bio-assays such as thymidine phosphorylase inhibition assay, urease inhibition assay, β-glucuronidase inhibition assays and cytotoxicity against PC-3 and HeLa cell lines.