Sulfonamide Schiff Base Research Articles

Synthesis, quantum chemical calculations, in silico and in vitro bioactivity of a sulfonamide-Schiff base derivative

The sulfonamide Schiff base compound (E)-4-((4-(dimethylamino)benzylidene)amino)-N-(5-methylisoxazol-3-yl)benzenesulfonamide was successfully prepared and fully characterized. The foremost objective of this study was to explore the molecular geometry of the aforementioned compound and determine its drug likeness characteristics, docking ability as an insulysin inhibitor, anticancer and antioxidant activities. The molecular structure of this compound was optimized using the B3LYP/6−311G+(d,p) level of theory. The compound was completely characterized utilizing both experimental and DFT approaches. Molecular electrostatic potential, frontier molecular orbitals, Fukui function, drug likeness, and in silico molecular docking analyses of this compound were performed. Wave functional properties such as localized orbital locator, electron localization function and non-covalent interactions were also simulated. The compound was screened for anticancer and antioxidant activities using in vitro technique. The observed FT-IR, UV–Vis, and 1H NMR results compared with simulated data and both results were fairly consistent. The experimental and computational spectral findings confirm the formation of the Schiff base compound. Both π—π* and n—π* transitions were observed in both experimental and computational UV–Vis spectra. The examined compound followed to Pfizer, Golden Triangle, GSK, and Lipinski's rules. Consequently, it possesses a more favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile, making it a suitable candidate for non-toxic oral drug use. Moreover, the compound exhibited promising insulysin inhibition activity in an in silico molecular docking. The compound showed in vitro anticancer activity against A549 cancer cells with an IC50 value of 40.89 μg/mL and moderate antioxidant activity.

Design and synthesis of oxazepine derivatives from sulfonamide Schiff bases as antimicrobial and antioxidant agents with low cytotoxicity and hemolytic prospective

The eco-friendly sonication and microwave irradiation techniques were used for the straight forward synthesis of the Schiff base platform from sulfathiazole. Herein, Schiff bases were developed and converted to oxazepane derivatives. Compounds were tested for their antimicrobial, antioxidant, in vivo cytotoxicity activity. Moreover, density functional theory (DFT) and molecular docking studies were also carried out to explore the structural prpoperties and interaction of compounds with the receptor molecules. In vitro antimicrobial activity was determined against Gram-positive and Gram-negative strains via microdilution technique, which showed that the synthesized derivatives exhibit significant antimicrobial activity. Furthermore, in vivo cytotoxicity activity of the compounds were carried out via intravenous injection in rats. The results were compared with negative controls and it was observed that most of the synthesized compounds displayed excellent antimicrobial activity and low toxicity in comparison to references and negative controls, respectively. Hemolysis test was carried out for bioactive compounds, and results showed higher hemolysis values of the Schiff bases than the correponding oxazepines and lower hemolytic effects. The free radical inhibittion and antioxidant activity was carried out by using 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH) and ferric reducing antioxidant power (FRAP) methods which suggested that the free radical scavenging activity increases with the presence of hydroxyl group. The Spectral measurements fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), and high resolution electrospray ionization mass spectrometry (HRESIMS) confirmed the structure of the compounds.

Design, molecular docking and antimicrobial assessment of newly synthesized p-cuminal-sulfonamide Schiff base derivatives

Antibiotic resistance of bacteria and fungi has been brewing for decades and has now surfaced as a potential public health emergency, globally. Thus, newer potent drug candidates are needed urgently to overcome antibiotic-resistant episodes. As an attempt to overcome the antimicrobial multi-drug resistance problems, a new series of p-cuminal sulfonamide Schiff base congeners 3a-3h were designed, synthesized, and their structures confirmed by several spectral studies. The antimicrobial activities assessment of obtained products was carried out against pathogenic bacteria Staphylococcus aureus, Streptococcus pyogenes, Methicillin-resistant Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and against pathogenic fungi Candida tropicalis and Trichophyton rubrum. Among them, 3b exhibited significant inhibition of all the strains of bacteria with MIC as 3.12μg/mL and the compound 3e exhibited the most promising control against both C. tropicalis and T. rubrum (MIC 6.25μg/mL) in comparison to Ketoconazole as well as good inhibition against both S. aureus and MRSA at MIC 6.25 μg/mL The presence of sulfamoyl and azomethine groups and some of heteroaryl rings in individual molecules could have increased the antibacterial actions, while the antifungal action could be attributed to the presence of guanyl and acetyl groups in the molecular structure. Furthermore, in silico investigation and drug-likeness have been ascertained with biological targets.

Synthesis, characterization, and biological evaluation of some 4-((thiophen-2-yl-methylene)amino)benzenesulfonamide metal complexes

BackgroundSulfonamides (sulfa drugs) and the metals like mercury, copper, and silver bear antimicrobial properties. The discovery of broad-spectrum antibiotics such as penicillins, cephalosporins, and fluoroquinolones has reduced their use. However, in some instances these drugs are the first-line treatment. The metal-based sulfonamide (e.g., silver sulfadiazine) is considered as first choice treatment in post-burn therapy while the use of silver nanoparticle-cephalexin conjugate to cure Escherichia coli infection explains the synergistic effect of sulfa drugs and their metal conjugates. With growing interest in metal-based sulfonamides and the Schiff base chemistry, it was decided to synthesize sulfonamide Schiff base metal complexes as antioxidant and antimicrobial agent.ResultsThe Fe (III), Ru (III), Co (II), Ni (II), Cu (II), Pd (II), Zn (II), Cd (II), and Hg (II) metal complexes of 4-((thiophen-2-ylmethylene)-amino)-benzenesulfonamide (TMABS) were prepared and studied for thermal stability, geometry, and other electronic properties. The ligand TMABS (Schiff base) and its metal complexes were screened in-vitro for 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and antimicrobial properties against Gram-positive (+ve) Bacillus subtilis (MTCC-441), Staphylococcus aureus (MTCC 7443), Gram-negative (-ve) Escherichia coli (MTCC 40), Salmonella typhi (MTCC 3231), and fungal strains Aspergillus niger (MTCC-1344) and Penicillium rubrum by agar well diffusion method. Results summarized in Tables 3, 4, and 5 represent the inhibitory concentration (IC50) in micromole (μM). The zone of inhibition (ZI) in millimeter (mm) represents antimicrobial properties of TMABS and its metal complexes.ConclusionsThe synthesized sulfanilamide Schiff base (TMABS) behaved as a neutral and bidentate ligand coordinating with metal ions through its azomethine nitrogen and thiophene sulfur to give complexes with coordination number of 4 and 6 (Fig. 3). The nucleophilic addition of sulfanilamide amino group (–NH2) group to carbonyl carbon (>C=O) of benzaldehyde gave sulfanilamide Schiff base (imine) (Fig. 2). All the metal complexes were colored and stable at room temperature. With IC50 of 9.5 ± 0.1 and 10.0 ± 0.7 μM, the Co, Cu, and Pd complexes appeared better antioxidant than the ligand TMABS (155.3±0.1 μM). The zone of inhibition (ZI) of Hg (28 mm) and Ru complexes (20 mm) were similar to the ligand TMABS (20 mm) against Aspergillus niger (MTCC-1344) as in Figs. 4, 5, and 6. None of the synthesized derivatives had shown better antimicrobial properties than the standard streptomycin sulfate and fluconazole.

Synthesis, characterization and antibacterial evaluation of some sulfonamide Schiff base derivatives

New series of Schiff base compounds obtained from sulfa drugs have been synthesized by the reaction of sulfonamide compounds (sulfadiazine, sulfapyridine, sulfamethazine, or sulfamerazine) with corresponding aromatic aldehydes (3-pyridinecarboxaldehyde or 4-pyridinecarboxaldehyde). The synthesized compounds were characterized by FT-IR, ESI-Mass, and 1H-NMR spectroscopy to confirm the chemical structures of synthesized compounds. The purity of all synthesized compounds were verified using pre-coated TLC (MERCK) plates using dichloromethane: methanol (9:1) solvent system. The chromatographic plates were viewed under ultraviolet(UV) light at 254 nm The sulfonamide Schiff base compounds were tested for antibacterial evaluation against two pathogenic Gram-positive bacteria (Staphylococcus aureus, Streptococcus spp.) and two pathogenic Gram-negative bacteria (Escherichia coli and Klebsiella pneumonia). The antibacterial activity of synthesized compounds was evaluated by assessing the inhibitory concentration by measuring their inhibition zone versus certain kinds of standard antibiotics with concentrations (500, 750, and 1000) μg /ml. Most synthesized compounds at high concentration were moderately active against all tested bacteria ,compound SH7 showed best antibacterial activity for both (Gram-positive and Gram-negative) bacteria while SH8 compound exhibited moderate antibacterial activity against Gram-positive bacteria and weak activity (<10 mm) against Gram-negative bacteria and all synthesized compounds were less antibacterial activity for all tested bacterial strains than standard drugs.

Synthesis, Characterization and Antimicrobial Activity of Two Novel Sulfonamide Schiff Base Compounds

Reactions of 2-hydroxy-3-methoxybenzaldehyde with p-toluenesulfonyl hydrazide and 4-nitrosulfonyl hydrazide under classical heating led to the corresponding sulfonamide Schiff bases 1 and 2. Both synthesized compounds were characterized by their spectroscopic data and elemental analysis. The antimicrobial activity of 1 and 2 against Gram-positive bacteria Staphylococcus epidermidis and Staphylococcus saprophyticus and Gram-negative bacteria Proteus mirabilis has been investigated by disc diffusion and minimum inhibitory concentration (MIC) methods. The disc diffusion method was also used to study antifungal activity of compounds against Aspergillus fumigates, Aspergillus clavatus, and Aspergillus flavus. Vancomycin and sulfamethoxazole/trimethoprim were used as standard drugs for bacteria and miconazole was used as antifungal standard.

Thermal decomposition and kinetic analyses of sulfonamide Schiff's bases in oxygen atmosphere - A comparative study

Two sulfonamide Schiff's bases namely, 4-(benzylideneamino)benzenesulfonamide (BABS) and 4-((4-methylbenzylidene)amino)benzenesulfonamide (4-MBABS) have been synthesized from benzaldehyde or 4-methylbenzaldehyde and 4-aminobenzenesulfonamide by condensation method and characterized by micro analysis, Fourier Transform Infrared and NMR (1H and 13C) techniques. The thermal decomposition of these compounds was studied by thermogravimetry/derivative thermogravimetry analysis (TG/DTG) under dynamic oxygen atmosphere at different heating rates of 10, 15 and 20 K min−1. The decomposition process of BABS is single step, whereas 4-MBABS followed two steps as evidenced from the data. The kinetic parameters were estimated using model-free (Friedman, Kissinger-Akahira-Sunose (KAS) and Flynn-Wall-Ozawa (FWO)) and model-fitting methods (Coats-Redfern (CR)). Invariant kinetic parameters are consistent with the average values obtained by Friedman and KAS isoconversional methods of these compounds. Each step decomposed in different kinetic models. The calculated thermodynamic parameters values show that the decomposition process is endothermic and non-spontaneous nature.

Non-isothermal decomposition of 4-((4-fluoro-3-phenoxy- benzylidene) amino) benzenesulfonamide under oxygen atmosphere

Abstract Sulfonamide Schiff's base namely, 4-((4-fluoro-3-phenoxybenzylidene) amino) benzene sulfonamide (4-FBABS) has been synthesized from 4-fluoro-3-phenoxybenzaldehyde, 4-aminobenzenesulfonamide and few drops of glacial acetic acid by condensation method and characterized by microanalysis, Fourier transform Infrared (FT-IR) and NMR ( 1 H and 13 C) spectroscopic techniques. The thermal decomposition of 4-FBABS was studied by thermogravimetry/derivative thermogravimetry analysis (TG-DTG) under dynamic oxygen atmosphere at different heating rates of 10, 15 and 20 K min −1 . The decomposition process of 4-FBABS is two steps as evidenced from thermogram. The kinetic parameters were estimated using model-free methods (Friedman, Kissinger–Akahira–Sunose (KAS) and Flynn–Wall–Ozawa (FWO)) and model-fitting method (Coats–Redfern (CR)). Invariant kinetic parameters of compound are consistent with the average values obtained by Friedman and KAS isoconversional methods of compound and each step decomposed in different kinetic models. The calculated ∆G ≠ values show that the decomposition processes are endothermic and non-spontaneous nature.

Synthesis, structure characterization and biological activity of selected metal complexes of sulfonamide Schiff base as a primary ligand and some mixed ligand complexes with glycine as a secondary ligand

The current work reports synthesis of metal complexes and mixed ligand complexes of a novel sulfonamide Schiff base ligand (HL) resulted from the condensation of sulfametrole [N′-(4-methoxy-1,2,5-thiadiazol-3-yl]sulfanilamide and acetyl-acetone as a primary ligand and glycine as a secondary ligand. The metal complexes and mixed ligand complexes of HL Schiff base ligand were synthesized and characterized using different physicochemical studies as elemental analyses, mass spectra, conductivity measurement, IR spectra, 1H NMR spectra, UV–vis Spectra, solid reflectance, magnetic susceptibility, thermal analyses (TGA and DTA) and their microbial and anticancer activities. The spectroscopic data of the complexes suggest their 1:2(L1:M) complex structures and 1:2:2(L1:L2:M) mixed ligand complex structures, where L1 = HL and L2 = glycine. Also, the spectroscopic studies suggested the octahedral structure for all complexes. The synthesized Schiff base, its metal and mixed ligand complexes were screened for their bacterial, antifungal and anticancer activity. The activity data show that the metal complexes and mixed ligand complexes exhibited promising microbial and anticancer activities than their parent HL Schiff base ligand, also the data show that the mixed ligand complexes more effective than the metal complexes.

ChemInform Abstract: Excellent Suzuki—Miyaura Catalytic Activity of a New Pd(II) Complex with Sulfonamide—Schiff Base Ligand.

AbstractThe novel catalyst exhibits excellent cross‐coupling activity.

Excellent Suzuki–Miyauracatalytic activity of a new Pd(II) complex with sulfonamide–Schiff base ligand

A new air‐stable Pd(II) complex containing a sulfonamide–Schiff base ligand has been synthesized, characterized and investigated as a catalyst for the Suzuki–Miyaura reactions of aryl halides with arylboronic acids. Theoretical calculations (B3LYP) and spectroscopic evidence suggest that the sulfonamide–Schiff base coordinates to the Pd centre through sulfonamide nitrogen (SO2NH2) rather than imine (CHN). The complex shows excellent cross‐coupling activity with aryl bromides in water at room temperature and aryl chlorides in isopropanol at 60°C. Copyright © 2016 John Wiley & Sons, Ltd.

Fluorescence sensing and intracellular imaging of Al3+ions by using naphthalene based sulfonamide chemosensor: structure, computation and biological studies

Naphthyl appended sulfonamide Schiff base (HL), an antimicrobial nontoxic agent, serves as a fluorogenic sensor to Al3+, LOD 33.2 nM and is used for living cell imaging.

Synthesis of novel Schiff base doped sol–gel silicas

Sulfonamide Schiff bases were doped uniformly in silica sol–gels prepared from liquid precursors by a fast and easy way at room temperature and processed to form xerogels. Schiff bases are efficient chelating agents, bioactive and catalytically active compounds. The structures of the newly synthesized Schiff base doped xerogels were elucidated by their physical (morphology, surface area, porosity), spectral (FTIR) and analytical (CHNSO/Si) data. The powder X-ray diffraction studies were carried out to confirm the formation of single phase. Characterization confirmed that Schiff base molecules are entrapped inside the pores as well as physically bound onto the silica surface. All Schiff base doped xerogels are stable mesoporous materials showing hydrophilic properties. Loadings of Schiff bases from 0.10 to 0.23 g/g of xerogel were obtained resulting amorphous materials. The doping of Schiff bases with xerogel caused change in surface area, pore volume and pore diameter of xerogel without damaging the main framework of siliceous skeleton. Morphology and colour of xerogel was also changed after doping. The entrapment of Schiff bases in xerogel caused increase in their decomposition temperatures. The final Schiff base doped xerogels show remarkable thermal stability.

Synthesis and Crystal Structures of Two Novel Complexes with N-[2-(5-Bromo-2-Hydroxybenzylideneamino)Ethyl]-4-Methylbenzenesulfonamide as Ligand

Two novel complexes constructed from the sulfonamide Schiff base ligand H 2 L, N-[2-(5-bromo-2-hydroxybenzylideneamino)ethyl]-4-methylbenzene-sulfonamide, [Cu(HL)2] (1) and [CuL(H2O)] (2) are synthesized and characterized via X-ray single-crystal diffraction, elemental analysis, FT-IR and UV–Vis. 1 and 2 both form 1-D supramolecular architectures by π–π stacking interactions. 1 and 2 both crystallize in monoclinic, with space group C2/c and P2/c for 1 and 2, with unit cell parameters a = 27.640(18) A, b = 7.907(5) A, c = 17.945(14) A, β = 118.27(2)°, V = 3454(4) A3, Z = 4 for 1, and a = 16.758(5) A, b = 7.272(2) A, c = 15.080(4) A, β = 106.334(5)°, V = 1763.6(9) A3, Z = 4 for 2. Two novel Cu(II) sulfonamide Schiff base complexes were prepared and characterized.

Synthesis, antitumor activity and molecular docking study of novel Sulfonamide-Schiff's bases, thiazolidinones, benzothiazinones and their C-nucleoside derivatives

A series of sulfapyridine-polyhydroxyalkylidene (or arylidene)-imino derivatives (Schiff's bases) 2a–c and 4a–e were prepared by condensation of 4-amino-N-pyridin-2-ylbenzenesulfonamide (1) with different monosaccharides or with aromatic aldehydes. Treatment of 2a–c with thioglycolic acid led to the formation of the C-nucleosides (3a–c), while treatment of 4a–e with thioglycolic and/or thiosalicylic acids afforded the corresponding 2-arylthiazolidin-4-one or 2-arylbenzothiazin-4-one derivatives 5a–e and/or 6a–e, respectively. Some representative examples of the newly prepared compounds showed considerable cytotoxic effect against breast carcinoma cell line MCF7 and cervix carcinoma cell line HELA in comparison with 5-flurouracil and doxorubicin. AutoDock molecular docking into PTK has been done for lead optimization of the compounds in study as potential PTK inhibitors.

Synthesis, crystal structures and characterization of two Cu(II) complexes with asymmetric sulfonamide Schiff-base ligands

Reaction of the N-tosyl-1,2-diaminopropane or N-tosyl-1,2-diaminobenzene with salicylaldehyde forms two new asymmetric sulfonamide Schiff bases, N-[2-(2-hydroxybenzylideneamino)propyl]-4-methylbenzenesulfonamide (H2L1 ) and N-[2-(2-hydroxybenzylideneamino)phenyl]-4-methylbenzenesulfonamide (H2L2 ). Two new complexes [CuL x (H2O)] (x = 1 for 1, x = 2 for 2) constructed from H2L x have been prepared and characterized via X-ray single-crystal diffraction, elemental analysis, FT-IR, UV-Vis, TGA, quantum chemical calculations, and photoluminescence measurements. Weak C–H ··· π, hydrogen bonds, π–π, and Cu ··· O weak interactions lead to 3-D supramolecular architecture, 1, and 1-D double chain, 2.

Synthesis, crystal structures and characterization of three novel complexes with N-[2-(2-hydroxybenzylideneamino)ethyl]-4-methyl-benzene-sulfonamide as ligand

Reaction of the N-tosyl-ethylenediamine and salicylaldehyde forms a new sulfonamide Schiff base N-[2-(2-hydroxybenzylideneamino)ethyl]-4-methyl-benzene-sulfonamide ( H 2L ). Three novel complexes constructed from H 2L , namely, [M( HL) 2] · xH 2O (M = Cu, x = 0 for 1, M = Ni, x = 0 for 2 and M = Zn, x = 1 for 3) have been prepared and characterized via X-ray single-crystal diffraction, elemental analysis, X-ray powder diffraction (XRPD), FT-IR, UV–Vis, TGA and photoluminescence measurements. Complex hydrogen bonds, C–H···π and π–π stacking interactions lead 1– 3 to present 1-D, 2-D and 3-D supramolecular architectures, respectively.

Some QSAR Studies for a Group of Sulfonamide Schiff Base as Carbonic Anhydrase CA II Inhibitors

In the present study, quantitative structure-activity-relationship (QSAR) study on a group of sulfonamide Schiff-base inhibitors of Carbonic Anhydrase (CA) enzyme has been carried out using Codessa Pro methodology and software. Linear regression QSAR models of the biological activity (Ki) of 38 inhibitors of carbonic anhydrase CA-II isozyme were established with 12 different molecular descriptors which were selected from more than hundreds of geometrical, topological, quantum-mechanical, and electronic types of descriptors and calculated using Codessa Pro software. Among the models presented in this study, statistically the most significant one is a five-parameter equation with correlation coefficient, R(2) values of ca. 0.840, and the cross-validated correlation coefficient, R(2) values of ca. 0.777. The obtained models allowed us to reveal some physicochemical and structural factors, which are strongly correlated with the biological activity of the compounds.