Ring transformation and complex formation of 3-acetyl-4,5-dihydro-1,2,4-triazole oximes

Oximic 1,2,4-triazole ligands 2a-e were prepared from the reaction of 3-acetyl-4,5-dihydro-1H-1,2,4-triazoles 1a-e with hydroxylamine hydrochloride at room temperature. At higher temperatures, the reaction afforded, however, the novel ring transformation product 4-amino-2-(4-chlorophenyl)-5-methyl-2H-1,2,3,6-oxatriazine 3. The reaction of the ligands 2a-e with nickel (II) and palladium (II) acetates in ethanol at room temperature yielded the respective square planar complexes 5a-e, 6a,e. X-ray structure determination of one of these complexes (5a) revealed that metallation led to unexpected ring transformation of the triazole ligand. It is probable that such ring transformation generated the imidazole-N-oxide intermediate 4a which coordinated to Ni(II) ion, and the 4N-donor set comprises both imidazole nitrogen and arylhydrazone nitrogen. The whole process is associated with loss of one hydrogen molecule and formation of one new π-bond. The new compounds were characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR and HRMS.     

Synthesis of regioisomeric 17β-N-phenylpyrazolyl steroid derivatives and their inhibitory effect on 17α-hydroxylase/C17,20-lyase

The reaction of 3β-hydroxy-21-hydroxymethylidenepregn-5-en-3β-ol-20-one (1) with phenylhydrazine (2a) affords two regioisomers, 17β-(1-phenyl-3-pyrazolyl)androst-3-en-3β-ol (5a) and 17β-(1-phenyl-5-pyrazolyl)androst-5-en-3β-ol (6a). The direction of the ring-closure reactions of 1 with p-substituted phenylhydrazines (2b-e) depends strongly on the electronic features of the substituents. Oppenauer oxidation of 3β-hydroxy-17β-exo-heterocyclic steroids 5a-e and 6a-e yielded the corresponding Δ⁴-3-ketosteroids 9a-e and 10a-e. The inhibitory effects (IC₅₀) of these compounds on rat testicular C_17,20-lyase were investigated by means of an in vitro radioligand incubation technique.     

Synthesis and evaluation of antioxidant and antibacterial activities of new substituted bis(1,3,4-oxadiazoles), 3,5-bis(substituted) pyrazoles and isoxazoles

Two series of five membered heterocyclic bis(1,3,4-oxadiazole) derivatives 2(a-h) and 3,5-bis(substituted)pyrazoles, isoxazoles 3(a,b,d-i), 4(a-c) were synthesized via oxidative cyclization of some diaroylhydrazones using chloramine-T and cyclocondensation reaction with hydrazine hydrate and hydroxylamine hydrochloride, respectively. The newly synthesized compounds were screened for antioxidant and anti-microbial activities. Compounds 2(b), 3(b), and 4(a) showed higher antioxidant activity at 10 μg/ml while compounds 2(a), 3(a), 3(f), and 4(a) exhibited better anti-microbial activity at 100 μg/ml compared with standard vitamin C and ciprofloxacin, respectively. Structures of newly synthesized compounds were confirmed by elemental analysis and spectral IR, ¹H NMR, and ¹³C NMR data.     

Ecdysteroids from Polypodium vulgare L

Three new compounds (3, 7, and 11) together with eight known phytoecdysteroids (1, 2, 4-6, and 8-10) were isolated from the rhizomes of common polypody, Polypodium vulgare L. The structures of compounds were elucidated by spectroscopic methods including 1D and 2D NMR measurements. The ¹H and ¹³C NMR assignments of compounds 1, 6, 9 and 10 are included.     

Anticancer and antifungal activity of copper(II) complexes of quinolin-2(1H)-one-derived Schiff bases

The condensation of substituted aromatic aldehydes with 7-amino-4-methyl-quinolin-2(1H)-one (1) has lead to the isolation of quinolin-2(1H)-one derived Schiff bases (2-14). The copper(II) complexes (2a-14a) of the ligands were also prepared, and together with their corresponding free ligands were fully characterised by elemental analyses, spectral methods (IR, ¹H and ¹³C NMR, AAS, UV-Vis), magnetic and conductance measurements. The bidentate ligands coordinated to the copper(II) ion through the deprotonated phenolic oxygen and the azomethine nitrogen of the ligands in almost all cases. X-ray crystal structures of two of the complexes, 5a and 8a, confirmed the bidentate coordination mode. All of the compounds were investigated for their antimicrobial activities against the fungus, Candida albicans, and against Gram-positive and Gram-negative bacteria. The compounds were found to have excellent anti-Candida activity but were inactive against Staphylococcus aureus and Escherichia coli. Selected compounds (2-8 and 2a-8a) were also screened for their in vitro anticancer potential using the human hepatic carcinoma cell line, Hep-G₂. Several derivatives were shown to be active comparable to that of cisplatin.     

Synthesis of 4,6-dideoxy-3-fluoro-2-keto-β-d-glucopyranosyl analogues of 5-fluorouracil, N-benzoyl adenine, uracil, thymine, N-benzoyl cytosine and evaluation of their antitumor activities

The synthesis of the unsaturated 4,6-dideoxy-3-fluoro-2-keto-β-d-glucopyranosyl nucleosides of 5-fluorouracil (6a), N⁶-benzoyl adenine (6b), uracil (6c), thymine (6d) and N⁴-benzoyl cytosine (6e), is described. Monoiodination of compounds 1a,b, followed by acetylation, catalytic hydrogenation and finally regioselective 2′-O-deacylation afforded the partially acetylated dideoxynucleoside analogues of 5-fluorouracil (5a) and N⁶-benzoyl adenine (5b), respectively. Direct oxidation of the free hydroxyl group at the 2′-position of 5a,b, with simultaneous elimination reaction of the β-acetoxyl group, afforded the desired unsaturated 4,6-dideoxy-3-fluoro-2-keto-β-d-glucopyranosyl derivatives 6a,b. Compounds 1c-e were used as starting materials for the synthesis of the dideoxy unsaturated carbonyl nucleosides of uracil (6c), thymine (6d) and N⁴-benzoyl cytosine (6e). Similarly a protection-selective deprotection sequence followed by oxidation of the free hydroxyl group at the 2′-position of the dideoxy benzoylated analogues 9c-e with simultaneous elimination reaction of the β-benzoyl group, gave the desired nucleosides 6c-e. None of the compounds was inhibitory to a broad spectrum of DNA and RNA viruses at subtoxic concentrations. The 5-fluorouracil derivative 6a was more cytostatic (50% inhibitory concentration ranging between 0.2 and 12 μM) than the other compounds.     

Synthesis and spectroscopic and X-ray structural characterisation of some para-substituted triaryltin(pentacarbonyl)manganese(I) complexes

A series of para-substituted triaryltin(pentacarbonyl)manganese(I) compounds [(p-XC₆H₄)₃SnMn(CO)₅: II, X=CH₃; III, X=CH₃O; IV, X=CH₃S; V, X=F; VI, X=Cl; VII, X=CH₃S(O₂)] is reported for comparison with the known phenyl analogue I. IR data [ν(CO)] as well as complete ¹¹⁹Sn/⁵⁵Mn/¹³C solution NMR results are given for I-VII. Chemical shifts, ¹¹⁹Sn versus ⁵⁵Mn, except I, correlate well, but have differing single parameter (SP) correlations, ¹¹⁹Sn versus σ_I and ⁵⁵Mn versus σ°_p. These results are compared with previous SP studies of the ¹¹⁹Sn solution NMR spectra of the series, (p-XC₆H₄)₄Sn and (p-XC₆H₄)₃SnY (Y=Cl, Br, I). Full crystal structures are reported for compounds II-VI. All are similar to that of I, with the Mn(CO)₅ moiety being a distorted tetragonal pyramid, and having a quasi-mirror plane through the central C₄MnSnC₃ skeleton. The Ar₃Sn are distorted trigonal propellers with ring torsion angles in the range 30-80°, the exception being IV with one torsion angle of 22°.     

Synthesis, spectroscopical characterization and the biological activity in vitro of new platinum(II) complexes with imidazo[1,5-a]-1,3,5-triazine derivatives and dimethylsulfoxide

A series of platinum(II) complexes with 6,8-dimethylimidazo[1,5-a]-1,3,5-triazin-4(3H)-one (6,8-DiMe-4-O-IMT) (I) and 6,8-dimethyl-2-thioxo-2,3-dihydroimidazo[1,5-a]-1,3,5-triazin-4(1H)-one (6,8-DiMe-4-O-2-S-IMT) (II) of formula trans-[PtCl₂(dmso)(6,8-DiMe-4-O-IMT)] (1a) and trans-[PtCl₂(dmso)(6,8-DiMe-4-O-2-S-IMT)] (2a) have been prepared and characterized with ¹H, ¹³C, ¹⁵N, ¹⁹⁵Pt NMR and IR. Significant ¹⁵N NMR upfield coordination shifts (81-96 ppm) of N(7) atom indicate this nitrogen atom as a coordination site. The multinuclear NMR and IR spectra indicate the square planar geometry with N(7) bonded heterocycles, S-bonded dimethylsulfoxide and two trans chloride anions. The platinum(II) complexes were tested for their antiproliferative activity in vitro against the cells of four human cell lines: SW707 rectal adenocarcinoma, A549 non-small cell lung carcinoma, T47D breast cancer and HCV29T bladder cancer. The activity of (1a, 2a) was lower than that of cisplatin.     

Sargachromanols as inhibitors of Na+/K+ ATPase and isocitrate lyase

Sargachromanols A-P (1-16), 16 meroterpenoids of the chromene class isolated from the brown alga Sargassum siliquastrum, were evaluated for their inhibitory activities toward Na⁺/K⁺ ATPase from porcine cerebral cortex and isocitrate lyase (ICL) from Candida albicans. These studies led to the identification of compounds 4, 6, 8, and 12 as potent Na⁺/K⁺ ATPase inhibitors. Compounds 12, 13, and 16 exhibited moderate ICL inhibitory activity. Compound 12 also showed weak antibacterial activity. The preliminary structure-activity relationship of these compounds is described to elucidate the essential structural requirements.     

Synthesis, characterization of [{(N-methyl-N-benzyl)amino}methyl]ferrocenes and their cyclopalladated complexes: Crystal structure of σ-Pd[(η-C5H5)Fe(η-C5H3CH2N(CH3)CH2C6H4NO2-4)]Cl(PPh3)

Condensation of aminomethylferrocene (1) and substituted benzaldehydes resulted in aldimines 2a-c which followed by reduction with sodium borohydride to give 3a-c. N-methylation of 3a-c with HCHO/NaCNBH₃/HOAc led to 4a-c. Treatment of 4a-c with sodium palladium tetrachloride in the presence of sodium acetate afforded cleanly cyclopalladated 5a-c in which configurations consisted of the R_NR_C, S_NS_C. The preferable activation of C_Ferrocenyl-H bond over C_Phenyl-H bond was also observed. All compounds 2-5 were characterized by elemental analysis, IR and ¹H NMR. In addition, the molecular structure of 5c was confirmed by single crystal X-ray diffraction. The possible mechanism for the formation of 5 was also discussed.     

Thermal solvent-free synthesis of novel pyrazolyl chalcones and pyrazolines as potential antimicrobial agents

A novel approach was adopted for the synthesis of series of new pyrazolyl chalcones (3a-c) by the reaction of 5-chloro-3-methyl-1-phenylpyrazole-4-carboxaldehyde (1) with different 5-acetylbarbituric acid derivatives (2a-c) under thermal solvent-free condition. The chalcones were then converted to the corresponding pyrazolines (4a-c) under the same condition in excellent yields. All the synthesized compounds were characterized using elemental analysis and spectral data (IR, ¹H NMR, and mass spectrometry). The synthesized compounds were tested for their antimicrobial activity by disk diffusion assay with slight modifications against Gram-positive, Gram-negative strains of bacteria as well as fungal strains. The investigation of antimicrobial screening revealed that compounds (3a-4c) showed good antibacterial and antifungal activities, respectively. Among the screened compounds, 3b showed more potent inhibitory activity (MIC = 12.5 μg/ml) nearly to that of standard antibiotics ciprofloxacin, griseofulvin and fluconazole.     

Dopamine release and molecular modeling study of some coumarin derivatives

4-aryl-2-amino-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)-pyridin-3-carbonitrile (1), 4-aryl-2-oxo-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)-pyridin-3-carbonitriles (2a-2c), 3-(6-aryl-1,2,5,6- tetrahydro-2-thioxopyrimidin-4-yl)-4-hydroxy-2H-chromen-2-one (3a, 3b) and pyrazol-3-yl-4-hydroxycoumarin derivatives (4a-4c, 5, 6a, 6b, 7a, 7b, and 8a-8c) were prepared in order to measure their % change dopamine release in comparison to amphetamine as reference, using PC-12 cells in different concentrations. In addition, the molecular modeling study of the compounds into 3BHH receptor was also demonstrated. The calculated inhibition constant (k_i) implemented in the AutoDock program revealed identical correlation with the experimental results to that obtained binding free energy (ΔG_b) as both parameters revealed reasonable correlation coefficients (R²) being 0.51 involving 10 compounds; (1, 2b, 2c, 3a, 3b, 4a, 4b, 6a, and 8c).     

Synthesis, structures and ligating properties of 2,6-bis(phosphino)thiophenol derivatives

New t-butyl-aryl thioethers where the aryl group is 2,6-bis(phosphino)phenyl have been synthesized. The syntheses were completed via sequential ortho-lithiations of t-butylphenylsulfide, followed by chlorophosphine (ClPR₂) quenches; symmetric (2,6-bis(diphenylphosphino)phenyl, (4a)) and unsymmetric (2-diisopropylphosphino-6-diphenylphosphino)phenyl, (4b) aryl groups were obtained. Treatment of 4a with Li or Na naphthalenide yielded 2,6-bis(diphenylphosphino)thiophenol 5. Reactions of 4a or 5 with NiCl₂ · 6H₂O yielded nickel bis(phosphinothiophenolate) 6. Compounds 4a,b, 5 and 6 were characterized by ¹H and ³¹P NMR, and by mass-spectrometry. In addition, 4a, 5 and 6 were characterized by single crystal X-ray diffraction methods.     

Synthesis, thermal and photophysical properties of phenoxy-substituted dendrimeric cyclic phosphazenes

In the present study, we describe the synthesis of a hydroxyl substituted bridged phenoxycyclotriphosphazene (5), [N₃P₃(OPh)₅OPhO(OPh)₅N₃P₃OPhOH], as a side group and its use for preparation of dendrimeric cyclic phosphazenes. For this purposes, compound 5 is synthesised in five steps from the reactions of cyclotriphosphazene with phenol derivatives. The dendrimeric compounds 6 and 7 have been prepared by the reactions of compound 5 with hexachlorocyclotriphosphazene, N₃P₃Cl₆, or octachlorocyclotetraphosphazene, N₄P₄Cl₈, respectively. Newly synthesized compounds have been fully characterized by elemental analysis, MALDI-TOF mass spectrometry, FT-IR, ¹H, ¹³C and ³¹P NMR spectroscopy. The thermal stability and fluorescence spectral properties of dendrimeric compounds 6 and 7 are investigated and compared with that of the previously reported cyclic compounds (I-II). Fluorescence quantum yields and lifetimes of dendrimeric compounds and their quenching behaviour by 1,4-benzoquinone are studied in dichloromethane.     

Methylated anthocyanidin glycosides from flowers of Canna indica

Methylated anthocyanin glycosides were isolated from red Canna indica flower and identified as malvidin 3-O-(6-O-acetyl-β-d-glucopyranoside)-5-O-β-d-glucopyranoside (1), malvidin 3,5-O-β-d-diglucopyranoside (2), cyanidin-3-O-(6″-O-α-rhamnopyranosyl-β-glucopyranoside (3), cyanidin-3-O-(6″-O-α-rhamnopyranosyl)-β-galactopyranoside (4), cyanidin-3-O-β-glucopyranoside (5) and cyanidin-O-β-galactopyranoside (6) by HPLC-PDA. Their structures were subsequently determined on the basis of spectroscopic analyses, that is, ¹H NMR, ¹³C NMR, HMQC, HMBC, ESI-MS, and UV-vis. Compounds (1-4) were found to be in major quantity while compounds (5-6) were in minor quantity.     

Macrocyclic dinuclear gold(I) and silver(I) NHCs complexes

The ligands bis-(imidazolium) hexafluorophosphate (Himy = -C₃N₂H₃-, imidazolium; R = 1-naphthylmethylene, 1a; 9-anthracenylmethylene, 1b) with an oxoether chain were easily prepared by the reaction of substituted imidazole with the diglycol diiodide, followed by exchange of anions with . 1a and 1b reacted with Ag₂O in DMSO or CH₃CN to yield [2 + 2] dinuclear Ag(I) NHCs macrocyclic complexes 2a and 2b, which showed much different conformation in solid corresponding to the R- substituent. Carbene transmetalation reactions of 2a-b with Au(SMe₂)Cl give dinuclear Au(I) analogs 3a and 3b. The new NHCs complexes were characterized by elemental analyses, ¹H NMR, ¹³C NMR and the structures of 2a-b and 3a were confirmed by X-ray diffraction determination.     

Synthesis and structure of titanium alkoxides based on tetraphenyl substituted 2,6-dimethanolpyridine moiety

Novel titanocanes and spirobititanocanes based on 2,6-bis[hydroxy(diphenyl)methyl]pyridine (1a) and 2,6-di(hydroxymethyl)pyridine (1b) - [2,6-C₅H₃N(CPh₂O)₂]Ti(O-i-Pr)₂ (2a), [2,6-C₅H₃N(CPh₂O)₂]₂Ti (3a), [2,6-C₅H₃N(CH₂O)₂]₂Ti (3b), [2,6-C₅H₃N(CPh₂O)₂]TiCl₂ (4) - as well as the closely related N-phenyl derivative PhN(CH₂CH₂O)₂Ti(Cl)Cp (5) have been synthesized. Complexes 2-5 were characterized by ¹H and ¹³C NMR spectroscopy and elemental analysis data. The molecular structure of 3a was determined by X-ray structure analysis.     

Synthesis of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives and their inhibition against growth of A549 and H322 lung cancer cells

A series of substituted pyrazolo[1,5-a]pyrazin-4(5H)-one was synthesized by the reaction of ethyl 1-(2-oxo-2-phenylethyl)-3-phenyl-1H-pyrazole-5-carboxylate derivatives and 2-(2-aminoethoxy)ethanol or 2-morpholinoethanamine in the condition of microwave-assisted one-step and solvent-free in a good yield. The structures of the compounds were determined by IR, ¹H NMR and mass spectroscopy. In addition, a representative single-crystal structure was characterized by using X-ray diffraction analysis. Preliminary biological evaluation showed that the compounds could inhibit the growth of A549 and H322 cells in dosage-dependent manners.     

Coordination compounds of Cd(II) with several bidentate-NN′ and tridentate-NN′N nitrogen donor ligands. Cd NMR studies of monomeric compounds containing nitrogen donor atoms

Reaction of CdCl₂ with N-alkylaminopyrazole ligands 1-[(2-ethylamino)ethyl]-3,5-dimethylpyrazole (deae), 1-[(2-(tert-butylamino)ethyl)]-3,5-dimethylpyrazole (deat), bis-[(3,5-dimethylpyrazolyl)methyl]ethylamine (bdmae), and bis-[(3,5-dimethylpyrazolyl)ethyl]ethylamine (ddae) in absolute ethanol yields [CdCl₂(NN′)] (NN′ = deae (1), deat (2)), [CdCl₂(bdmae)] (3), and [CdCl(ddae)]₂[CdCl₄] (4). The Cd(II) complexes have been characterised by elemental analyses, conductivity measurements, IR, ¹H, ¹³C{¹H} and ¹¹³Cd NMR spectroscopies, and X-ray diffraction methods. ¹H and ¹¹³Cd NMR experiments at variable temperature for 3 and 4 show that dynamic processes are taking place in solution. We report the measurements of ¹¹³Cd NMR chemical shift data for complexes 1-4 in solution. X-ray crystal structures for complexes 2 and 3 have been determined. The Cd(II) is coordinated to the deat ligand, in 2, by one nitrogen atom of the pyrazolyl group and one nitrogen atom of the amine. It finishes a tetrahedral geometry with two chlorine atoms. The bdmae ligand is linked to Cd(II), in 3, by two nitrogens atoms of the pyrazolyl groups and one amine nitrogen, along with two chlorine atoms, in a distorted trigonal bipyramidal geometry.     

Synthesis and characterization of some α,ω-bis(naphthylseleno)alkanes: X-ray crystal structure of 1,2-bis(1-naphthylseleno)ethane

α,ω-Bis(naphthylseleno)alkanes [C₁₀H₇Se(CH₂)_nSeC₁₀H₇] (1a-c), where n = 1-3, have been prepared through two different methods. One of the two methods involves the alkylation of sodium 1-naphthylselenolate, generated by the Se-Se bond reduction of dinaphthyl diselenide using hydrazine hydrate while the other involves the reaction of in situ generated α-naphthylselenomagnesium bromide with the appropriate dihaloalkane. The synthesized α,ω-bis(naphthylseleno)alkanes (1a-c) have been characterized with the help of elemental analysis and various spectroscopic techniques viz., multinuclear NMR (¹H, ¹³C, ⁷⁷Se), IR, UV-Vis spectroscopy and mass spectrometry. X-ray crystallographic results and molecular geometry of 1,2-bis(1-naphthylseleno)ethane (1b) has also been illustrated.