Synthesis,Characterization, Biological Evaluation and DNA Interaction Studies of 4-Aminophenol Derivatives: Theoretical and Experimental Approach

In the present study, five 4-aminophenol derivatives (4-chloro-2-(((4-hydroxyphenyl)imino)methyl)phenol(S-1), 4-((4-(dimethylamino)benzylidene)amino)phenol(S-2), 4-((3-nitrobenzylidene)amino)phenol(S-3), 4-((thiophen-2-ylmethylene)amino)phenol(S-4) and 4-(((E)-3-phenylallylidene)amino)phenol(S-5)) were synthesized and characterized by FT-IR, ¹H-NMR, ¹³C-NMR and elemental analyses. The synthesized compounds were tested for their antimicrobial (Gram-positive and Gram-negative bacteria and Saccharomyces cervesea fungus) and antidiabetic (α-amylase and α-glucosidase inhibitory) activities. All the compounds showed broad-spectrum activities against the Staphylococcus aureus (ATCC 6538), Micrococcus luteus (ATCC 4698), Staphylococcus epidermidis (ATCC 12228), Bacillus subtilis sub. sp spizizenii (ATCC 6633), Bordetella bronchiseptica (ATCC 4617) and Saccharomyces cerevisiae (ATCC 9763) strains. The newly synthesized compounds showed a significant inhibition of amylase (93.2%) and glucosidase (73.7%) in a concentration-dependent manner. Interaction studies of Human DNA with the synthesized Schiff bases were also performed. The spectral bands of S-1, S-2, S-3 and S-5 all showed hyperchromism, whereas the spectral band of S-4 showed a hypochromic effect. Moreover, the spectral bands of the S-2, S-3 and S-4 compounds were also found to exhibit a bathochromic shift (red shift). The present studies delineate broad-spectrum antimicrobial and antidiabetic activities of the synthesized compounds. Additionally, DNA interaction studies highlight the potential of synthetic compounds as anticancer agents. The DNA interaction studies, as well as the antidiabetic activities articulated by the molecular docking methods, showed the promising aspects of synthetic compounds.     

Synthesis,antimicrobial, anticancer,antiviral evaluation and QSAR studies of 4-(1-aryl-2-oxo-1,2-dihydro-indol-3-ylideneamino)-N-substituted benzene sulfonamides

A series of 4-(1-aryl-2-oxo-1,2-dihydro-indol-3-ylideneamino)-N-substituted benzenesulfonamide derivatives (1–32) was synthesized and evaluated for its in vitro antimicrobial, antiviral and cytotoxic activities. Antimicrobial results indicated that compounds (11) and (18) were found to be the most effective ones. In general, the synthesized compounds were bacteriostatic and fungistatic in their action. The cytotoxic screening results indicated that the compounds were less active than the standard drug 5-fluorouracil (5-FU). None of the compounds inhibited viral replication at subtoxic concentrations. In general, the presence of a pyrimidine ring with electron releasing groups and an ortho- and para-substituted benzoyl moiety favored antimicrobial activities. The results of QSAR studies demonstrated the importance of topological parameters, valence zero order molecular connectivity index (⁰χ^v) and valence first order molecular connectivity index (¹χ^v) in describing the antimicrobial activity of synthesized compounds.     

Synthesis,Identification, Computer-Aided Docking Studies,and ADMET Prediction of Novel Benzimidazo-1,2,3-triazole Based Molecules as Potential Antimicrobial Agents

2-azido-1H-benzo[d]imidazole derivatives 1a,b were reacted with a β-ketoester such as acetylacetone in the presence of sodium ethoxide to obtain the desired molecules 2a,b. The latter acted as a key molecule for the synthesis of new carbazone derivatives 4a,b that were submitted to react with 2-oxo-N-phenyl-2-(phenylamino)acetohydrazonoyl chloride to obtain the target thiadiazole derivatives 6a,b. The structures of the newly synthesized compounds were inferred from correct spectral and microanalytical data. Moreover, the newly prepared compounds were subjected to molecular docking studies with DNA gyrase B and exhibited binding energy that extended from −9.8 to −6.4 kcal/mol, which confirmed their excellent potency. The compounds 6a,b were found to be with the minimum binding energy (−9.7 and −9.8 kcal/mol) as compared to the standard drug ciprofloxacin (−7.4 kcal/mol) against the target enzyme DNA gyrase B. In addition, the newly synthesized compounds were also examined and screened for their in vitro antimicrobial activity against pathogenic microorganisms Staphylococcus aureus, E. coli, Pseudomonas aeruginosa, Aspergillus niger, and Candida albicans. Among the newly synthesized molecules, significant antimicrobial activity against all the tested microorganisms was obtained for the compounds 6a,b. The in silico and in vitro findings showed that compounds 6a,b were the most active against bacterial strains, and could serve as potential antimicrobial agents.     

Synthesis, characterization, and biological evaluation of new oxime-phosphazenes

Hexachlorocylotriphosphazene (1) was reacted with 4-hydroxy-3-methoxybenzaldehyde to give hexakis[(4-formyl-2-methoxy)phenoxy]cyclotriphosphazene (2). Hexakis[(4-(hydroxyimino)2-methoxy)phenoxy]cyclotriphosphazene (3) was synthesized by reaction of 2 with hydroxlamine hydrochloride in pyridine. Compound 3 was reacted with benzyl chloride, acetyl chloride, allyl bromide, benzoyl chloride, propanoyl chloride, 4-methoxybenzoyl chloride, 2-chlorobenzoyl chloride, chloroacetyl chloride, methyl iodide, and thiophene-2-carbonyl chloride. From these reactions, full or partially substituted compounds were obtained, usually in high yields. Pure or defined products could not be obtained from reaction of 3 with methacryloyl chloride and O-acetylsalicyloyl chloride. The structures of the compounds were determined by elemental analysis, and IR, ¹H, ¹³C, and ³¹P NMR spectroscopy. The synthesized compounds were screened for in-vitro antimicrobial activity against two Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis), two gram-negative bacteria (Escherichia coli and Klebsiella pneumonia), and fungal strains (Aspergillus niger, and Candida albicans) by the agar well diffusion method. Few compounds had significant activity against both Gram-positive and Gram-negative bacteria. None of the compounds had antifungal activity except compounds 7 and 9, which had moderate activity.     

Synthesis,characterization, DNA binding,antibacterial, and antioxidant activity of new bis-phthalimides

New bis-phthalimides were synthesized by 2: 1 condensation of phthalic anhydride and tetrachlorophthalic anhydride with 1,2,4-triazole-3,5-diamine, pyridine-2,6-diamine, and 4-hydroxypyrimidine- 2,6-diamine. The synthesized compounds were characterized by elemental analyses and IR, ¹H NMR, and mass spectra. Their interaction with calf thymus DNA (ct-DNA) was studied by UV-Vis spectrophotometry, cyclic voltammetry, and viscosity measurements, which revealed intercalative mode of binding to ct-DNA. Antibacterial activity of the synthesized compounds against Escherichia coli and Streptococcus mutans was assessed in vitro by the agar well diffusion method. The antioxidant activity of these compounds was estimated by DPPH assay.     

Synthesis,characterization and antimicrobial evaluation of 2,5-disubstituted-4-thiazolidinone derivatives

In the present study novel derivatives of 4-thiazolidinone were prepared from biphenyl-4-carboxylic acid and evaluated for their in vitro antimicrobial activity against two Gram negative strains (Escherichia coli and Pseudomonas aeruginosa) and two Gram positive strains (Bacillus subtilis and Staphylococcus aureus) and fungal strain Candida albicans and Aspergillus niger. The newly synthesized compounds were characterized by IR, ¹H NMR and C, H, N analyses. The results revealed that all synthesized compounds have a significant biological activity against the tested microorganisms. Among the synthesized derivatives 4g (biphenyl-4-carboxylic acid [2-(3-bromophenyl)-5-(3-nitrobenzylidene)-4-oxo-thiazolidin-3-yl]-amide) and 4i (biphenyl-4-carboxylic acid [5-(3-bromobenzylidene)-2-(3-bromophenyl)-4-oxo-thiazolidin-3-yl]-amide) were found to be most effective antimicrobial compounds.     

Synthesis,characterization and antimicrobial activities of new bis-hydrazonothioxothiazolidinone derivatives

New bis-hydrazonothioxothiazolidinone derivatives based on 2-thioxothiazolidin-4-one were synthesized in good yields using a simplified experimental condition. The structure of synthesized compounds was established with the help of common physico-chemical analysis and various spectroscopic techniques like FT-IR, mass and ¹H NMR. The results of characterizations are in good agreement with the proposed structure of all the synthesized compounds. Further, the antimicrobial (antibacterial and antifungal) activities of all the synthesized derivatives were carried out against various species like Bacillus subtilis, Escherichia coli, Aspergillous niger and Aspergillous flavus by using agar-cup method. The results of antimicrobial screening showed that all the compounds have mild to moderate activity. However, some of the compounds (3a, 3b, 3d, 3e, 3f, 3g, 3i and 3j) have shown better activity than the other.     

<em>N</em>-Substituted 5-Chloro-6-phenylpyridazin-3(2<em>H</em>)-ones: Synthesis, Insecticidal Activity Against <em>Plutella xylostella </em>(L.) and SAR Study

A series of N-substituted 5-chloro-6-phenylpyridazin-3(2H)-one derivatives were synthesized based on our previous work; all compounds were characterized by spectral data and tested for in vitro insecticidal activity against Plutella xylostella. The results showed that the synthesized pyridazin-3(2H)-one compounds possessed good insecticidal activities, especially the compounds 4b, 4d, and 4h which showed > 90% activity at 100 mg/L. The structure-activity relationships (SAR) for these compounds were also discussed.     

Ln(Fe3+M2+)O4 compounds with layer structure [Ln : Y,Er, Tm,Yb, and Lu, M : Mg,Mn, Co,Cu, and Zn]

A series of new compounds Ln(Fe³⁺M²⁺)O₄ [Ln : Y, Er, Tm, Yb, and Lu, M : Mg, Mn, Co, Cu, and Zn] were successfully synthesized and their lattice constants were determined. These compounds have the same crystal structure as YbFe₂O₄ and Fe³⁺ and M²⁺ are both surrounded by five oxygen ions forming a trigonal bipyramid. The synthetic conditions are presented. They are strongly dependent upon the constituent cations of the compound.     

Cytotoxicity, antioxidant, and antimicrobial activities of novel 2-quinolone derivatives derived from coumarin

Coumarins are important and useful compounds with diverse pharmacological properties. New coumarin derivatives namely N-aminoquinoline-2-one 1, 1-((4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)methyleneamino)quinolin-2(1H)-one 2 and 1,1′-(1E,1′E)-(1,4-phenylenebis(methan-1-yl-1-ylidene))bis(azan-1-yl-1-ylidene)diquinolin-2(1H)-one 3, were synthesized and characterized by UV–Vis, FT-IR, and NMR spectra in addition of elemental analysis. The synthesized compounds (2 and 3) show considerable anticancer activity against HEp-2 cell line. Synthesized compounds (2 and 3) were tested against selected types of microbial organisms and showed significant activities. The free-radical scavenging activity of synthesized compounds (2 and 3) have been determined by their interaction with the stable free-radical 1,1-diphenyl-2-picrilhydrazyl (DPPH) and all the compounds have shown encouraging antioxidant activities.     

Solvent-Free Synthesis,In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens

A new series of 1,3,4-thiadiazoles was synthesized by the reaction of methyl 2-(4-hydroxy-3-methoxybenzylidene) hydrazine-1-carbodithioate (2) with selected derivatives of hydrazonoyl halide by grinding method at room temperature. The chemical structures of the newly synthesized derivatives were resolved from correct spectral and microanalytical data. Moreover, all synthesized compounds were screened for their antimicrobial activities using Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Bacillus subtilis, Staphylococcus aureus, and Candida albicans. However, compounds 3 and 5 showed significant antimicrobial activity against all tested microorganisms. The other prepared compounds exhibited either only antimicrobial activity against Gram-positive bacteria like compounds 4 and 6, or only antifungal activity like compound 7. A molecular docking study of the compounds was performed against two important microbial enzymes: tyrosyl-tRNA synthetase (TyrRS) and N-myristoyl transferase (Nmt). The tested compounds showed variety in binding poses and interactions. However, compound 3 showed the best interactions in terms of number of hydrogen bonds, and the lowest affinity binding energy (−8.4 and −9.1 kcal/mol, respectively). From the in vitro and in silico studies, compound 3 is a good candidate for the next steps of the drug development process as an antimicrobial drug.     

Synthesis,antimicrobial activity and docking study of some novel 4-(4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino derivatives carrying biologically active sulfonamide moiety

A new series of 4-((4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino)-N-(substituted)benzenesulfonamide 3–17, monosubstituted 2-((4-((4-aminophenyl)sulfonyl)phenyl)amino)methylene 18, and its disubstituted derivative 19 were synthesized from the starting material 2-((dimethylamino)methylene)-5,5-dimethylcyclohexane-1,3-dione 2. The crystal structures of compounds 2, 7 and 13 were reported by us through X-ray crystallography. All the prepared compounds were evaluated for their antibacterial activity against Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, Clostridium sporogenes), Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli), and antifungal activity against Aspergillus fumigatus, Penicillium chrysogenum, Fusarium oxysporum, Candida albicans. The synthesized compounds displayed interesting antimicrobial activity. Compounds 4 and 12 were the most potent in this study and displayed higher activity compared to the reference drugs, with MIC value of 3.9–31.3 μg/mL against a panel of Gram-positive, Gram-negative bacteria and fungi. Molecular modeling was performed inside the active site of dihydropteroate synthase. The synthesized compounds showed similar orientation and binding interactions to that of the co-crystallized ligand inside the binding pocket.     

Ultrasound-assisted,one-pot,three-component synthesis and antibacterial activities of novel indole derivatives containing 1,3,4-oxadiazole and 1,2,4-triazole moieties

Thirteen novel indole derivatives were efficiently synthesized through ultrasound irradiation by using 4-amino-5-(1H-indol-3-yl)-4H-[1,2,4]triazole-3-thiol (8) and 2-mercapto-5-substituted-1,3,4-oxadiazoles (5a–m). Compared with conventional and microwave methods, yields increased to 82–93%, and reaction times decreased to 15–35 min. The structures of these novel compounds were characterized by spectral data and elemental analysis. Two out of the synthesized compounds (10f and 10l) exhibited excellent activity against Staphylococcus aureus and Escherichia coli, and thus warrant further research.     

Synthesis,characterization, antibacterial activities and carbonic anhydrase enzyme inhibitor effects of new arylsulfonylhydrazone and their Ni(II), Co(II) complexes

Ethane sulfonic acide hydrazide (esh: CH₃CH₂SO₂NHNH₂) derivatives as 5-methylsalicyl-aldehydeethanesulfonylhydrazone (5msalesh), 5-methyl-2-hydroxyacetophenoneethane sulfonylhydrazone (5mafesh) and their Ni(II), Co(II) complexes have been synthesized for the first time. The structure of these compounds has been investigated by elemental analysis, FT-IR, ¹H NMR, ¹³C NMR, LC/MS, UV–vis spectrophotometric method, magnetic susceptibility, thermal studies and conductivity measurements. The antibacterial activities of synthesized compounds were studied against Gram positive bacteria; Staphylococcus aureus, Bacillus subtilis, Bacillus magaterium and Gram negative bacteria; Salmonella enteritidis, Escherichia coli by using the microdilution broth method. The biological activity screening showed that ligands have more activity than complexes against the tested bacteria. The inhibition activities of these compounds on carbonic anhydrase II (CA II) have been investigated by comparing IC₅₀ and K_i values and it has been found that 5msalesh and its complexes have more enzyme inhibition efficiency than other compounds.     

Synthesis,characterization and antibacterial activity of some new pyrazole based Schiff bases

In the present study a series of new Schiff bases were synthesized. All the synthesized compounds were characterized by IR, ¹H NMR, mass spectral and elemental analyses. Newly synthesized compounds were screened for their antibacterial (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) activity. The results revealed that, compounds 3f and 3c have exhibited significant biological activity against the tested microorganisms.     

Synthesis and biological evaluation of some novel pyrazole,isoxazole, benzoxazepine,benzothiazepine and benzodiazepine derivatives bearing an aryl sulfonate moiety as antimicrobial and anti-inflammatory agents

A new series of pyrazole, isoxazole, benzoxazepine, benzothiazepine and benzodiazepine derivatives were prepared by the multi-component cyclo-condensation reaction of 1-phenyl-3-(2-(tosyloxy)phenyl)propane-1,3-dione, N,N-dimethylformamide dimethyl acetal and hydrazine or hydroxylamine hydrochloride or 2-aminothiophenol or 2-aminophenol or benzene-1,2-diamine using μwave technique in aqueous media. All the synthesized compounds were evaluated for their anti-bacterial and antifungal activities. Some of the selected compounds were also screened for their anti-inflammatory activity.     

Rhodanine-based biologically active molecules: synthesis,characterization, and biological evaluation

To investigate the antimicrobial properties of the rhodanine (2-thioxo-4-thiazolidinone) structure, several 2-[(5Z)-5-benzylidene-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-N-phenylacetamide derivatives were synthesized by use of an efficient procedure. Variation of the functional group on the 5-benzylidine ring of rhodanine led to compounds containing a 2-thioxo-4-thiazolidinone group attached to N-phenyl acetamide. The chemical structures of the compounds were confirmed by IR, ¹H NMR, and ¹³C NMR spectroscopy, ESI mass spectrometry, and elemental analysis. The antibacterial and antifungal activity of the compounds were tested, at seven concentrations, against Gram-positive bacterial strains (Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 25922), Gram-negative bacterial strains (Staphylococcus aureus ATCC 25923 and Bacillus subtilis ATCC 11774), and fungal strains (Candida albicans ATCC 66027 and Aspergillus niger ATCC 6275), by use of the Kirby Bauer disk-diffusion technique and the serial broth dilution technique. The results obtained were compared with those for reference drugs. Relationships between structure and their antimicrobial activity are discussed.     

Synthesis of novel fluorinated benzothiazol-2-yl-1,2,4-triazoles: Molecular docking,antifungal evaluation and in silico evaluation for SAR

Lead hybridization concept was used to design and synthesize twenty novel hybrid compounds by combining fungicidal leads viz. 6-flouro-1,3-benzothiazol-2-amine and 1,2,4-triazoles in a single molecule, with the aim of discovery of high potential novel fungicides. Antifungal evaluation of synthesized 6-flourobenzothiazol-2-yl-1,2,4-triazoles against various phytopathogenic fungi revealed synergistic effect of combination of leads with one another in all the test compounds. Some of the synthesized compounds showed excellent fungitoxicity comparable with the standard fungicides used. In silico toxicity of all the compounds was equivalent to the standard fungicides used. Docking studies and Lipinski filtration were performed in order to present the rationale of structure activity relation. Compounds 2, 8, 15 and 18 were screened to act as leads for further modification and use.     

Design, synthesis and utilization of a novel coupling reagent for the preparation of O-alkyl hydroxamic acids

An efficient novel reagent, phosphoric acid diethyl ester 2-phenyl-benzimidazol-1-yl ester, was designed, and synthesized and its applicability was demonstrated for the preparation of O-alkyl hydroxamic acids. The O-alkyl hydroxamic acids of N-protected amino acids were also synthesized. The enantiomeric purity of the synthesized compounds were measured using chiral HPLC and the degree of racemization was found to be negligible.