Characterization of Antimicrobial, Antioxidant, and Leishmanicidal Activities of Schiff Base Derivatives of 4-Aminoantipyrine.

Our main interest is the characterization of compounds to support the development of alternatives to currently marketed drugs that are losing effectiveness due to the development of resistance. Schiff bases are promising biologically interesting compounds having a wide range of pharmaceutical properties, including anti-inflammatory, antipyretic, and antimicrobial activities, among others. In this work, we have synthesized 12 Schiff base derivatives of 4-aminoantipyrine. In vitro antimicrobial, antioxidant, and cytotoxicity properties are analyzed, as well as in silico predictive adsorption, distribution, metabolism, and excretion (ADME) and bioactivity scores. Results identify two potential Schiff bases: one effective against E. faecalis and the other with antioxidant activity. Both have reasonable ADME scores and provides a scaffold for developing more effective compounds in the future. Initial studies are usually limited to laboratory in vitro approaches, and following these initial studies, much research is needed before a drug can reach the clinic. Nevertheless, these laboratory approaches are mandatory and constitute a first filter to discriminate among potential drug candidates and chemical compounds that should be discarded.

Synthesis and Evaluation of Curcuminoid Analogues as Antioxidant and Antibacterial Agents.

Diazocoupling reaction of curcumin with different diazonium salts of p-toluidine, 2-aminopyridine, and 4-aminoantipyrine in pyridine yielded the arylhydrazones 2a-c. Arylhydrazone of p-toluidine reacted with urea, thiourea, and guanidine nitrate to produce 5,6-dihydropyrimidines. Further reaction of 2a with 2,3-diaminopyrdine in sodium ethoxide solution yielded 1H-pyrido[2,3-b][1,4]diazepine derivative. Bis(2,5-dihydroisoxazole) is obtained from the reaction of 2a with hydroxylamine hydrochloride, while its reactions with hydrazines afforded the respective 4,5-dihydro-1H-pyrazoles. The target compounds were evaluated as antioxidant and antibacterial agents. The tested compounds showed good to moderate activities compared to ascorbic acid and chloramphenicol, respectively.

Design, Synthesis, Spectral Analysis, In Vitro Anticancer Evaluation and Molecular Docking Studies of Some Fluorescent 4-Amino-2, 3-Dimethyl-1-Phenyl-3-Pyrazolin-5-One, Ampyrone Derivatives.

The commenced work deals with the synthesis, characterization and evaluation of biological activities of 4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one. The synthesis was done by the condensation of aromatic acid chlorides with 4-aminoantipyrine. The structures of synthesized derivatives were elucidated using IR, Mass, 1H NMR and 13C NMR spectroscopy, and their UV-Visible and fluorescence properties were studied. The compounds showed significant dual fluorescence. Molecular docking was used to understand the small molecule-receptor protein interaction. The derivatives were screened for their in vitro cytotoxic activity against the reference drug pazopanib on human cervical cancer cell line (SiHa) using MTT assay.

Synthesis and spectroscopic characterization of fluorescent 4-aminoantipyrine analogues: Molecular docking and in vitro cytotoxicity studies.

Two substituted aromatic carbonyl compounds (compounds 1 and 2) of 4-aminoantipyrine were synthesized by condensation of fluorine substituted benzoyl chlorides and 4-aminoantipyrine. The structures of synthesized derivatives were established on the basis of UV-Vis, IR, and Mass, (1)H, (13)C NMR and Fluorescence spectroscopy. Both compounds showed significant fluorescence emission and two broad emission bands were observed in the region at 340 nm and 450 nm on excitation at 280 nm. Theoretically to prove that the molecule has anticancer activity against cervical cancer cells, the compounds were analyzed for molecular docking interactions with HPV16-E7 target protein by Glide protocol. Furthermore, 4-aminoantipyrine derivatives were evaluated for their in vitro cytotoxic activity against human cervical cancer cells (SiHa) by MTT assay. Compound 1 showed two fold higher activity (IC50=0.912 µM) over compound 2, and its activity was similar to that of Pazopanib, suggesting that although the two compounds were chemically very similar the difference in substituent on the phenyl moiety caused changes in properties.

Synthesis, characterization and anti-breast cancer activity of new 4-aminoantipyrine-based heterocycles.

4-Aminoantipyrine was utilized as key intermediate for the synthesis of pyrazolone derivatives bearing biologically active moieties. The newly synthesized compounds were characterized by IR, 1H- and 13C-NMR spectral and microanalytical studies. The compounds were screened as anticancer agents against a human tumor breast cancer cell line MCF7, and the results showed that (Z)-4-((3-amino-5-imino-1-phenyl-1H-pyrazol-4(5H)-ylidene)methylamino)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 5, 3-(4-bromophenyl) -1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 13, 1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-3-(4-iodophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 14, 3,3'-(4,4'-sulfonylbis(4,1-phenylene))bis(1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile) 16, (Z)-1- (1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-hydrazono-4-oxo-3-phenyl-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 17, (Z)-1-(1,5-dimethyl-3-oxo-2-phenyl- 2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-3-phenyl-2-(2-phenylhydrazono)-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile 18, and (Z)-4-(3-amino-6-hydrazono-7-phenyl-6,7-dihydro pyrazolo[3,4-d]pyrimidin-5-yl)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 19 were the most active compounds with IC50 values ranging from 30.68 to 60.72 µM compared with Doxorubicin as positive control with the IC50 value 71.8 µM.

Efficient interrupting skills of amino acid metallointercalators with DNA at physiological pH: evaluation of biological assays.

The 4-aminoantipyrine derivatives (NO2, OCH3) and their mixed-ligand complexes with amino acids have been synthesized and investigated for their binding with CT DNA using UV-visible spectroscopy, cyclic voltammetry, and viscosity measurements under physiological conditions of pH (stomach 4.7; blood 7.4). The results from all techniques i.e. binding constant (Kb), and free energy change (ΔG) were in good agreement and inferred spontaneous compound-DNA complexes formation via intercalation. Among all the compounds 1 and 4 showed comparatively greater binding at pH 7.4 as evident from its greater Kb values. All the complexes exhibit oxidative cleavage of supercoiled (SC) pBR322 plasmid DNA in the presence of H2O2 as an activator. It is remarkable that at 25µM concentration 1 and 4 completely degrade SC DNA into undetectable minor fragments and thus they act as efficient chemical nucleases. Among the new complexes, complexes 1 and 4 have highest potential against all the microorganisms tested. The results of the above biological experiments also reveal that the choice of different metal ions has little influence on the DNA binding, DNA cleavage and antimicrobial assay.

New hydrazones with pyrazolone structure: synthesis, characterization and biological evaluation.

AIM: To design new hydrazones with pyrazolone structure with improved biological properties. MATERIAL AND METHODS: New hydrazones of antipyrine have been prepared by reaction of 4-aminophenazone (4-aminoantipyrine) with chloracetylchoride and hydrazine hydrate and then condensation with various aromatic aldehydes. RESULTS: The synthesized compounds were screened for their antibacterial activity against Gram positive (Staphylococcus aureus ATCC 25923, Sarcinalutea ATCC 9341, Bacillus cereus ATCC 14579, Bacillus subtilis) and Gram negative bacterial strains (Escherichia coli ATCC 25922) and pathogenic yeasts (Candida albicans ATCC 10231, Candida sake, Candidaglabrata). Some of them were found to have good antibacterial and antifungal activity. The antioxidant activity of these compounds was also evaluated using the total antioxidant capacity test. CONCLUSIONS: The chemical modulations performed on antipyrine structure have a good influence on the biological activity of the synthesized compounds.

Synthesis, spectral characterization and biological activity of metal(II) complexes with 4-aminoantipyrine derivatives.

Novel metal(II) complexes derived from furfurylidene-4-aminoantipyrine and 2-aminobenzothiazole were synthesized and characterized by spectroscopic (IR, (1)H NMR, UV-Vis., ESR and DART-MS) and other analytical methods. IR spectral studies indicate the binding sites of the ligand with the metal ion. Molar conductance data and magnetic susceptibility measurements provide evidence for monomeric and neutral nature of the complexes. The X band ESR spectrum of the Cu(II) complex at 300 and 77K was recorded. The electrochemical behaviour of the complexes in MeCN at 298 K was studied. Thermal studies of the ligand and its complexes show the presence of coordinated water in the complexes. The grain size of the complex was calculated by Scherrer formula using powder XRD. The surface morphology of the complexes was studied using SEM. The in vitro biological screening of the ligand and its complexes were tested against bacterial species S. aureus, E. coli, K. pneumoniae, P. vulgaris and P. aeruginosa and fungal species A. niger, R. stolonifer, A. flavus, R. bataicola and C. albicans. The DNA binding and cleavage activity of the ligand and its complexes were studied. Super oxide dismutase (SOD) activities of the ligand and its complexes have also been measured.

Synthesis, crystal structure, vibration spectral, and DFT studies of 4-aminoantipyrine and its derivatives.

Three compounds derived from 4-aminoantipyrine (AA) were synthesized and their structures confirmed by melting point, elemental analysis, FT-IR, and 1H-NMR. The molecular structures of the four compounds were characterized by single-crystal X-ray diffraction and calculated by using the density functional theory (DFT) method with 6-31G (d) basis set. The calculated molecular geometries and the vibration frequencies of the AA derivatives in the ground state have been compared with the experimental data. The results show that the optimized geometries can reproduce well the crystal structural parameters, and the theoretical vibration frequencies show good agreement with the experimental data, although the experimental data are different from the theoretical ones due to the intermolecular forces. Besides, the molecular electrostatic potential (MEP) and the frontier molecular orbital (FMO) analysis of the compounds were investigated by theoretical calculations.

Supramolecular and structural modification on conformational by mixed ligand.

A novel series of platinum(II) and palladium(II) complexes have been synthesized by template condensation of 4-methoxybenzaldehyde, benzaldehyde, 4-chlorobenzaldehyde and 4-nitrobenzaldehyde, with appropriate 4-aminoantipyrine (4-AAP) in the presence of K(2)PtCl(4)/PdCl(2) to form complexes of the type [M(L(n))Cl(2)](where M=Pt(II) or Pd(II)). The corresponding Schiff base complexes mixed ligand were prepared by condensation of [M(L(n))Cl(2)] with ethanolamine (LH). The complexes have been characterized with the help of elemental analysis, IR, (1)H and (13)C NMR, electronic spectra, conductance measurements, magnetic susceptibilities and thermal analysis. On the basis of these studies, it is clear that ligands coordinated to metal atom in a mononuclear (NO) in (1-6), Schiff base complexes (NN(*)) in (7-9) and monobasic tridentate Schiff base complexes (NN(*)O) in (10-12). Thus, suitable square planar geometry for tetradentated state has been suggested for the metal complexes. Various ligand and nephelouxetic parameter have been calculated for the complexes. The thermal decomposition for complexes was studied.

Synthesis of novel Schiff base analogues of 4-amino-1,5-dimethyl-2-phenylpyrazol-3-one and their evaluation for antioxidant and anti-inflammatory activity.

4-Aminoantipyrine (4-amino-1,5-dimethyl-2-phenylpyrazole-3-one) and its analogues have been found to be compounds of interest for their anti-inflammatory, analgesic, antiviral, antipyretic, antirheumatic and antimicrobial activities. In the present study, Schiff base analogues of 4-aminoantipyrine were synthesized by the condensation reaction with substituted benzaldehydes and then evaluated for their antioxidant and anti-inflammatory activities. From among the synthesized compounds (3a-m, 4 and 5), 3 k and 3f exhibited the highest antioxidant activity followed by 3g, 3l, 3c, 3i, 5, 3m and 3h. The IC(50) values for compounds 3 k and 3f were found to be 0.44 and 0.93 µM, respectively, comparable to that of ascorbic acid (IC(50) 0.41 µM), a standard antioxidant agent. From the comparisons between the hydroxylated and methoxylated compounds, the rank order of antioxidant activity for the products resulting from benzylidene phenyl ring substitution was 2,4,6-OH>3,4-OH>3-OMe-4-OH>3,5-OMe-4-OH>2,4-OH>3-Me-4-OMe>3,4-OMe>4-OMe>4-OH. The structure-activity relationship study revealed that the position and nature of the substituted group on the benzylidene phenyl ring of the Schiff base analogues of 4-aminoantipyrine play an important role in their antioxidant activity. The anti-inflammatory activity of 3f, which also exhibited excellent antioxidant activity, was evaluated in terms of its inhibition of NO production, an inflammatory modulator, in LPS pretreated RAW 264.7 cells using the Griess method. We also examined whether or not this compound had effect on iNOS and COX-2 mRNA expression in RAW 264.7 cells. It was observed that compound 3f significantly reduced NO production and inhibited LPS-stimulated iNOS and COX-2 mRNA levels in a dose-dependent manner. Overall, 3f showed promising antioxidant and anti-inflammatory activities and may be used as the lead compound in a future study.

Experimental and theoretical studies on 4-(2,4-dichlorobenzylideneamino)antipyrine and 4-(2,6-dichlorobenzylideneamino)antipyrine.

Two antipyrine derivates, with the same formula C(18)H(15)Cl(2)N(3)O, are structurally similar Schiff bases derived from the condensation of 2,4-dichlorobenzaldehyde or 2,6-dichlorobenzaldehyde and 4-aminoantipyrine in methanol solutions. The compounds were characterized by elemental analysis, FT-IR, FT-Raman and UV-vis techniques. Density functional calculations were performed to further optimize and characterize them. The calculated results indicate that the theoretical values show good agreements with experimental ones. They are similar in their IR spectra and different in their Raman spectra. The detailed vibrational and UV-vis absorption spectra of the compounds have been ascribed to their corresponding molecular structures and electrons orbital transitions. The statistical thermodynamic functions and their correlations with temperatures of the title compounds have been obtained from their theoretical vibrations of the optimized structures. The nonlinear optical and UV-vis properties indicate that the compounds are the promising photoelectronic materials.