Synthesis and Characterization of Novel 1,3-Diaryltriazene-Substituted Sulfaguanidine Derivatives as Selective Carbonic Anhydrase Inhibitors: Biological Evaluation, in Silico ADME/T and Molecular Docking Study.

Sulfonamide compounds known as human carbonic anhydrase (hCA) inhibitors are used in the treatment of many diseases such as epilepsy, antibacterial, glaucoma, various diseases. 1,3-diaryl-substituted triazenes and sulfaguanidine are used for therapeutic purposes in many drug structures. Based on these two groups, the synthesis of new compounds is important. In the present study, the novel 1,3-diaryltriazene-substituted sulfaguanidine derivatives (SG1-13) were synthesized and fully characterized by spectroscopic and analytic methods. Inhibitory effect of these compounds on the hCA I and hCA II was screened as in vitro. All the series of synthesized compounds have been identified as potential hCA isoenzymes inhibitory with KI values in the range of 6.44±0.74-86.85±7.01 nM for hCA I and with KI values in the range of 8.16±0.40-77.29±9.56 nM for hCA II. Moreover, the new series of compounds showed a more effective inhibition effect than the acetazolamide used as a reference. The possible binding positions of the compounds with a binding affinity to the hCA I and hCA II was demonstrated by in silico studies. In conclusion, compounds with varying degrees of affinity for hCA isoenzymes have been designed and as selective hCA inhibitors. These compounds may be potential alternative agents that can be used to treat or prevent diseases associated with glaucoma and hCA inhibition.

ZnO and Au nanoparticles supported highly sensitive and selective electrochemical sensor based on molecularly imprinted polymer for sulfaguanidine and sulfamerazine detection.

This study aimed to develop a molecularly imprinted polymer (MIP) sensor using electropolymerization of thiophene acetic acid monomer around template molecules, sulfaguanidine (SGN) and sulfamerazine (SMR), for selective and sensitive detection of both antibiotics. Au nanoparticles were then deposited on the modified electrode surface, and SGN and SMR were extracted from the resulting layer. Surface characterization, changes in the oxidation peak current of both analytes, and investigation of the electrochemical properties of the MIP sensor were examined using scanning electron microscopy, cyclic voltammetry, and differential pulse voltammetry. The developed MIP sensor with Au nanoparticles showed a detection limit of 0.030 µmol L-1 and 0.046 µmol L-1 for SGN and SMR, respectively, with excellent selectivity in the presence of interferents. The sensor was successfully used for SGN and SMR analysis in human fluids, including blood serum and urine, with excellent stability and reproducibility.

Nature of Luminescence and Pharmacological Activity of Sulfaguanidine.

Sulfonamides are one of the oldest groups of veterinary chemotherapeutic agents. Physico-chemical properties, the concentration and the nature of the environment are the factors responsible for the distribution of sulfonamides in the living organism. Although these drug compounds have been in use for more than half a century, knowledge about their behavior is still limited. Physiological activity is currently attributed to the sulfanyl radical. Our study is devoted to the spectral properties of aqueous solutions of sulfaguanidine, in which the formation of complexes with an H-bond and a protonated form takes place. The nature of the fluorescent state of sulfaguanidine was interpreted using computational chemistry, the electronic absorption method and the luminescence method. The structure of sulfaguanidine includes several active fragments: aniline, sulfonic and guanidine. To reveal the role of fragments in the physiological activity of the studied antibiotic, we calculated and compared the effective charges of the fragments of aniline and sulfaguanidine molecules. Chromophore groups were identified in molecules, which determine the intermolecular interaction between a molecule and a proton-donor solvent. The study also revealed the impact of sulfone and guanidine groups, as well as complexation, on the effective charge of the antibiotic fragment responsible for physiological activity and luminescent ability.

Monitoring of trace aquatic sulfonamides through hollow zinc-nitrogen-carbon electrocatalysts anchored on MXene architectures.

Herein, we designed and fabricated hollow N-doped carbon polyhedrons with atomically dispersed Zn species (Zn@HNCPs) through a topo-conversion strategy by utilising metal-organic frameworks as precursors. Zn@HNCPs achieved efficient electrocatalytic oxidation of sulfaguanidine (SG) and phthalyl sulfacetamide (PSA) sulfonamides through the high intrinsic catalytic activity of the Zn-N4 sites and excellent diffusion from the hollow porous nanostructures. The combination of the novel Zn@HNCPs with two-dimensional Ti3C2Tx MXene nanosheets resulted in improved synergistic electrocatalytic performance for the simultaneous monitoring of SG and PSA. Therefore, the detection limit of SG for this technique is much lower than those of other reported techniques; to the best of our knowledge, this is the first detection approach for PSA. Moreover, these electrocatalysts show promise for the quantification of SG and PSA in aquatic products. Our insights and findings can serve as guidelines for the development of highly active electrocatalysts for application in next-generation food analysis sensors.

Effect of hydrophobic extension of aryl enaminones and pyrazole-linked compounds combined with sulphonamide, sulfaguanidine, or carboxylic acid functionalities on carbonic anhydrase inhibitory potency and selectivity.

Design and synthesis of three novel series of aryl enaminones (3a-f and 5a-c) and pyrazole (4a-c) linked compounds with sulphonamides, sulfaguanidine, or carboxylic acid functionalities were reported as carbonic anhydrase inhibitors (CAIs) using the "tail approach" strategy in their design to achieve the most variable amino acids in the middle/outer rims of the hCAs active site. The synthesised compounds were assessed in vitro for their inhibitory activity against the following human (h) isoforms, hCA I, II, IX, and XII using stopped-flow CO2 hydrase assay. Enaminone sulphonamide derivatives (3a-c) potently inhibited the target tumour-associated isoforms hCA IX and hCA XII (KIs 26.2-63.7 nM) and hence compounds 3a and 3c were further screened for their in vitro cytotoxic activity against MCF-7 and MDA-MB-231 cancer cell lines under normoxic and hypoxic conditions. Derivative 3c showed comparable potency against both MCF-7 and MDA-MB-231 cancer cell lines under both normoxic ((IC50 = 4.918 and 12.27 µM, respectively) and hypoxic (IC50 = 1.689 and 5.898 µM, respectively) conditions compared to the reference drug doxorubicin under normoxic (IC50 = 3.386 and 4.269 µM, respectively) and hypoxic conditions (IC50 = 1.368 and 2.62 µM, respectively). Cell cycle analysis and Annexin V-FITC and propidium iodide double staining methods were performed to reinforce the assumption that 3c may act as a cytotoxic agent through the induction of apoptosis in MCF-7 cancer cells.

Exploring the cytotoxic effect and CDK-9 inhibition potential of novel sulfaguanidine-based azopyrazolidine-3,5-diones and 3,5-diaminoazopyrazoles.

Regarding the structural analysis of variable effective CDK-9 suppressors, we record the design and synthesis of two new sets of sulfaguanidine-based azopyrazolidine-3,5-diones and 3,5-diaminoazopyrazoles with expected anticancer and CDK-9 inhibiting activity. In the designed molecules, the pyrazole ring and sulphaguanidine fragment were linked together for the first time through diazo linkers as they are expected to enhance the anticancer activity and CDK degrading interaction. All derivatives have been estimated regarding their cytotoxic activity toward three tumor cells where CDK overexpression has been reported (HePG2, HCT-116, and MCF-7). Among these, four derivatives VII, VIII, X, and XIII exerted potent cytotoxicity against the chosen tumor cells presenting IC50 range equal to 2.86-25.89 µM. As well cytotoxicity on non-cancer cells and CDK-9 inhibition assay have been also assessed for these candidates to evaluate their selectivity indices and enzyme inhibition. The 3,5-diaminopyrazole-1-carboxamide derivative XIII showed a superior combined profile as cytotoxic with high selectivity toward cancer cells (HePG2: IC50 = 6.57 µM, SI = 13.31; HCT-116: IC50 = 9.54 µM, SI = 9.16; MCF-7: IC50 = 7.97 µM, SI = 10.97). Accordingly, it has been chosen to evaluate its probable mechanistic effect both in vitro (via enzyme assay, apoptosis induction, and cell cycle study) as well as in silico (through molecular docking). Overall, this work introduces the 3,5-diaminopyrazole-1-carboxamide derivative XIII as a potent CDK-9 inhibitor candidate (IC50 = 0.16 µM) that merits further investigations for the management of breast, colorectal, and hepatic malignancies.

Inhibition Studies on Carbonic Anhydrase Isoforms I, II, IX, and XII with a Series of Sulfaguanidines.

Two novel sulfaguanidine series, six N-(N,N'-dialkyl/dibenzyl-carbamimidoyl) benzenesulfonamide derivatives and nine N-(N-alkyl/benzyl-carbamimidoyl) benzenesulfonamide derivatives, were obtained by desulfidative amination of easily accessible dimethyl arylsulfonylcarbonimidodithioates under catalyst- and base-free conditions. The newly synthesized compounds were tested for the inhibition of four different isozymes of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). Both series reported here were inactive against the off-target isozymes hCA I and II (Ki >100 µM). Interestingly, all investigated compounds inhibited both target isozymes hCA IX and XII in the submicromolar to micromolar ranges in which Ki values spanned from 0.168 to 0.921 µM against hCA IX and from 0.335 to 1.451 µM against hCA XII. The results indicated that N-(N-alkyl/benzyl-carbamimidoyl) benzenesulfonamides were slightly more potent inhibitors than N-(N,N'-dialkyl/dibenzyl-carbamimidoyl) benzenesulfonamides. Among the evaluated compounds, N-n-octyl-substituted N-carbamimidoylbenzenesulfonamide showed the most significant activity with a Ki value of 0.168 µM against hCA IX, which was four-fold more selective toward this isozyme versus hCA XII. Again, another derivative from N-(N-alkyl/benzyl-carbamimidoyl) benzenesulfonamide series, N-p-methylbenzyl-substituted N-carbamimidoylbenzenesulfonamide, demonstrated superior inhibitory activity against hCA XII with a Ki value of 0.335 µM.

Novel bis-ureido-substituted sulfaguanidines and sulfisoxazoles as carbonic anhydrase and acetylcholinesterase inhibitors.

To discover alternative substances to compounds used to treat many diseases, especially treating Alzheimer's disease (AD) and Parkinson's disease targeting carbonic anhydrase (hCA) and acetylcholinesterase (AChE) enzymes, is important. For this purpose, a series of novel bis-ureido-substituted sulfaguanidine (SG1-4) and sulfisoxazole (SO1-4) derivatives were synthesized, and their inhibitory capacities were screened against hCA isoenzymes (hCA I and II) and AChE. Possible binding mechanisms of inhibitors to the active site were elucidated by in silico studies, and the results were supported by in vitro results. Moreover, the percent radical scavenging capacities of the derivatives were also evaluated. The derivatives (SG1-4 and SO1-4) were more effective against hCAs compared to standard drug acetazolamide (KI values of 98.28-439.17 nM for hCA I and II, respectively) and exhibited the highest inhibition with the KIs in the ranges of 2.54 ± 0.50-41.02 ± 7.52 nM for hCA I, 11.20 ± 2.97-67.14 ± 13.58 nM for hCA II, and 257.60 ± 27.84-442.60 ± 52.13 nM for AChE. Also, compounds SG1 and SO1 also showed ABTS radical scavenging activity at the rate of 70% and 78%, respectively. These results will contribute to the literature for the rational design and synthesis of new potent and selective inhibitors targeting hCAs and AChE with multifunctional effects such as radical scavenging as well as inhibition. This study focused on the synthesis and inhibitory effects of bis-ureido-substituted sulfaguanidine (SG1-4) and sulfisoxazole (SO1-4) derivatives against human hCA I and II isoforms and AChE. In order to test synthesized derivatives' free radical scavenging potentials were the DPPH and ABTS assays. In silico studies elucidated possible binding mechanisms of inhibitors to the active site.

The comprehensive effects of aluminum oxide nanoparticles on the physiology of freshwater microalga Scenedesmus obliquus and it's phycoremediation performance for the removal of sulfacetamide.

Nanoparticles are inevitable byproducts of modern industry. However, the environmental impacts arising from industrial applications of nanoparticles are largely under-reported. This study evaluated the ecotoxicological effects of aluminum oxide nanoparticles (Al2O3NP) and its influence on sulfacetamide (SA) biodegradation by a freshwater microalga, Scenedesmus obliquus. Although Al2O3NP showed limited toxicity effect on S. obliquus, we observed the toxicity attenuation aspect of Al2O3NP in a mixture of sulfacetamide on microalgae. The addition of 100 mg L-1 of Al2O3NP and 1 mg L-1 of SA reduced total chlorophyll by 23.3% and carotenoids by 21.6% in microalgal compared to control. The gene expression study demonstrated that ATPF0C, Lhcb1, HydA, and psbA genes responsible for ATP synthesis and the photosynthetic system were significantly downregulated, while the Tas gene, which plays a major role in biodegradation of organic xenobiotic chemicals, was significantly upregulated at 1 and 100 mg L-1 of Al2O3NP. The S. obliquus removed 16.8% of SA at 15 mg L-1 in 14 days. However, the removal was slightly enhanced (18.8%) at same concentration of SA in the presence of 50 mg L-1 Al2O3NP. This result proves the stability of sulfacetamide biodegradation capacity of S. obliquus in the presence of Al2O3NP co-contamination. The metabolic analysis showed that SA was degraded into simpler byproducts such as sulfacarbamide, sulfaguanidine, sulfanilamide, 4-(methyl sulfonyl)aniline, and N-hydroxy-benzenamine which have lower ecotoxicity than SA, demonstrating that the ecotoxicity of sulfacetamide has significantly decreased after the microalgal degradation, suggesting the environmental feasibility of microalgae-mediated wastewater technology. This study provides a deeper understanding of the impact of nanoparticles such as Al2O3NP on aquatic ecosystems.

Synthesis, Characterization, and Inhibition Study of Novel Substituted Phenylureido Sulfaguanidine Derivatives as α-Glycosidase and Cholinesterase Inhibitors.

A series of six N-carbamimidoyl-4-(3-substituted phenylureido)benzenesulfonamide derivatives were synthesized by reaction of sulfaguanidine with aromatic isocyanates. In vitro and in silico inhibitory effects of the novel ureido-substituted sulfaguanidine derivatives were investigated by spectrophotometric methods for α-glycosidase (α-GLY), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes associated with diabetes mellitus (DM) and Alzheimer's disease (AD). N-Carbamimidoyl-4-{[(3,4-dichlorophenyl)carbamoyl]amino}benzene-1-sulfonamide (2f) showed AChE and BChE inhibitory effects, with KI values of 515.98±45.03 nM and 598.47±59.18 nM, respectively, while N-carbamimidoyl-4-{[(3-chlorophenyl)carbamoyl]amino}benzene-1-sulfonamide (2e) showed strong α-GLY inhibitory effect, with KI values of 103.94±13.06 nM. The antidiabetic effects of the novel synthesized compounds are higher than their anti-Alzheimer's effects, because the inhibition effect of the compounds on the α-GLY with diabetic enzyme is greater than the effect on esterase enzymes. Indeed, inhibition of the metabolic enzymes is important for the treatment of DM and AD.

Rapid detection of sulfaguanidine in fish by using a photonic crystal molecularly imprinted polymer.

A photonic crystal (PC) sensor was prepared through molecular imprinting by using dispersed SiO2 microspheres as PC, sulfaguanidine (SG) as template, methacrylic acid as monomer, and ethylene glycol dimethacrylate as crosslinker. The preparation conditions were optimized as follows: molar ratio of template, monomer, and crosslinker was 1:10:4; pH was 6.0 in phosphate buffer; and volume fraction of methanol was 15%. The relationship between wavelength shift of reflection peak and SG concentration was found as: Δλ = 7.8887 lg(C) + 79.9664. The response time was only 5 min. The limit of detection was 2.8 × 10-10 mol L-1. The sensor exhibited higher specificity for SG than its sulfonamide analogs. The sensor maintained original sensing performance after five cycles of usage. The recoveries of SG ranged from 93.8% to 111.2% in lake water and from 88.5% to 115.2% in fish samples. This finding suggested that the sensor can be used in food samples with complicated matrix.

Compounds with Potential Activity against Mycobacterium tuberculosis.

The high acquisition rate of drug resistance by Mycobacterium tuberculosis necessitates the ongoing search for new drugs to be incorporated in the tuberculosis (TB) regimen. Compounds used for the treatment of other diseases have the potential to be repurposed for the treatment of TB. In this study, a high-throughput screening of compounds against thiol-deficient Mycobacterium smegmatis strains and subsequent validation with thiol-deficient M. tuberculosis strains revealed that ΔegtA and ΔmshA mutants had increased susceptibility to azaguanine (Aza) and sulfaguanidine (Su); ΔegtB and ΔegtE mutants had increased susceptibility to bacitracin (Ba); and ΔegtA, ΔmshA, and ΔegtB mutants had increased susceptibility to fusaric acid (Fu). Further analyses revealed that some of these compounds were able to modulate the levels of thiols and oxidative stress in M. tuberculosis This study reports the activities of Aza, Su, Fu, and Ba against M. tuberculosis and provides a rationale for further investigations.

Sulfaguanidine cocrystals: Synthesis, structural characterization and their antibacterial and hemolytic analysis.

Sulfaguanidine (SG), belongs to the class of sulfonamide drug used as an effective antibiotic. In the present work, using crystal engineering approach two novel cocrystals of SG were synthesized (SG-TBA and SG-PT) with thiobarbutaric acid (TBA) and 1,10-phenanthroline (PT), characterized by solid state techniques viz., powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and the crystal structures were determined by single crystal X-ray diffraction studies. A comparative antibacterial activity and hemolytic potential was done on SG drug, coformers and their cocrystals. The tested cocrystals formulations showed almost two fold higher antibacterial activity against the tested strains of bacteria Gram-positive bacteria (S. mutans and E. faecalis) and Gram-negative bacteria (E. coli, K. pneumonia and E. clocae) over SG alone and their coformers. Cocrystal SG-TBA showed better antibacterial activity and reduced hemolysis, thereby, reduced cytotoxicity than SG-PT.

Antimicrobial sulfonamides clear latent Kaposi sarcoma herpesvirus infection and impair MDM2-p53 complex formation.

Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8, is the causative agent of Kaposi sarcoma; this malignant angiosarcoma is usually treated with conventional antitumor agents that can control disease evolution, but do not clear the latent KSHV episome that binds to cellular DNA. Some commercial antibacterial sulfonamides were tested for the ability to suppress latent KSHV. Quantitative PCR (qPCR) and cytofluorometry assays were used for detecting both viral DNA and the latency factor LANA (latency-associated nuclear antigen) in BC3 cells, respectively. The capacity of sulfonamides to impair MDM2-p53 complex formation was detected by an enzyme-linked immunosorbent assay method. The analysis of variance was performed according to one-way analysis of variance with Fisher as a post hoc test. Here we show that sulfonamide antibiotics are able to suppress the KSHV latent state in permanently infected BC3 lymphoma cells and interfere with the formation of the MDM2-p53 complex that KSHV seemingly needs to support latency and to trigger tumor cell transformation. These findings detected a new molecular target for the activity of sulfonamides and offer a new potential perspective for treating KSHV-induced lymphoproliferative diseases.

Three-component synthesis and carbonic anhydrase inhibitory properties of novel octahydroacridines incorporating sulfaguanidine scaffold.

Novel sulfaguanidines incorporating acridine moiety were synthesized by the reaction of cyclohexane-1,3-dione, sulfaguanidine, and aromatic aldehydes. Synthesis of these compounds was performed in water at room temperature, and their structures were confirmed by using spectral analysis (IR, 1H-NMR, 13C-NMR, and HRMS). Human carbonic anhydrase isoenzymes (hCA I and II) were purified from erythrocyte cells with affinity chromatography. hCA I was purified 83.40-fold with a specific activity, 1060.9 EU mg protein-1, and hCA II was purified 262.32-fold with a specific activity, 3336.8 EU mg protein-1. The inhibitory effects of newly synthesized sulfaguanidines and acetazolamide, (AAZ) as a control compound, on hydratase and esterase activities of these isoenzymes have been studied in vitro. Synthesized compounds have moderate inhibition potentials on hCA I and hCA II isoenzymes. IC50 values of compounds for esterase activity are in the range of 118.4 ± 7.0 µM-257.5 ± 5.2 µM for hCA I and 86.7 ± 3.0 µM-249.4 ± 10.2 µM for hCA II, respectively.

Preparation and application of sulfaguanidine-imprinted polymer on solid-phase extraction of pharmaceuticals from water.

The molecularly imprinted polymers (MIPs) with sulfaguanidine as a template, methacrylic acid, 4-vinylpyridine, and 2-hydroxyethyl methacrylate as functional monomers, ethylene glycol dimethacrylate as a cross-linker and 2,2'-azobis-isobutyronitrile as an initiator have been prepared through the cross-link reaction of polymerization. Solid-phase extraction (SPE) procedure for the extraction of sulfaguanidine from water samples using the prepared MIPs and non-imprinted (NIPs) was evaluated. The best MIP in combination with commercial sorbents was applied for simultaneous extraction of eight pharmaceuticals. New SPE cartridges were prepared by combination of optimal produced MIP and Oasis HLB in 6 mL of polypropilene SPE reservoir. The developed method which includes new SPE cartridge (MIPMAA-Oasis HLB, 400mg/6 mL) and thin-layer chromatography was validated. The method provides a linear response over the concentration range of 0.5-150 µg/L, depending on the pharmaceutical with the correlation coefficients>0.9843 in all cases except for norfloxacin (0.9770) and penicillin G procaine (0.9801). Also, the method has revealed low limits of detection (0.25-20 µg/L), good precision (intra and inter-day), a relative standard deviation below 15% and recoveries above 95% for all eight pharmaceuticals. The developed method by using newly prepared SPE cartridge has been successfully applied to the analysis of production wastewater samples from pharmaceutical industry.

Thermodynamic studies for adsorption of ionizable pharmaceuticals onto soil.

Although pharmaceutical compounds (PCs) are being used more and more widely, and studies have been carried out to assess their presence in the environment, knowledge of their fate and behavior, especially under different environmental conditions, is still limited. The principle objective of the present work, therefore, is to evaluate the adsorption behavior of three ionizable, polar compounds occurring in different forms: cationic (propranolol - PRO), anionic (sulfisoxazole - SSX) and neutral (sulfaguanidine - SGD) onto soil under various temperature conditions. The adsorption thermodynamics of these researched compounds were extensively investigated using parameters such as enthalpy change (ΔH°), Gibbs free energy change (ΔG°) as well as entropy change (ΔS°). These calculations reveal that sorption of PRO is exothermic, spontaneous and enthalpy driven, sorption of SGD is endothermic, spontaneous and entropy driven whereas sorption of SSX is endothermic, spontaneous only above the temperature of 303.15K and entropy driven. Furthermore, we submit that the calculated values yield valuable information regarding the sorption mechanism of PRO, SGD and SSX onto soils.

Column and batch tests of sulfonamide leaching from different types of soil.

Sulfonamides (SAs) and their metabolites present severe hazards to human health and the environment, mainly because of antibiotic resistance. Knowledge of their bioavailability, including their sorption to soils and their impact on the soil-groundwater pathway, is crucial to their risk assessment. Laboratory batch and column leaching tests are important tools for determining the release potential of contaminants from soil or waste materials. Batch and column tests were carried out with soils differing in particle size distribution, organic matter content and pH, each spiked with sulfonamides (sulfadimethoxine (SDM), sulfaguanidine (SGD), sulfisoxazole (SX)). In order to test the applicability of leaching tests to polar contaminants batch and column tests were also compared. In the column tests, release was found to depend on the properties of both soil and sulfonamides. The fastest release was observed for coarse-grained soil with the smallest organic matter content (MS soil; 100% decrease in concentration until liquid-to-solid ratio (L/S) of 0.9 L kg(-1) for all SAs). The slowest release was established for sulfadimethoxine (24.5% decrease in concentration until L/S 1.22 L kg(-1)). The results of the batch and column tests were comparable to a large extent, with slightly higher concentrations being obtained in the column test experiments of fine-grained soils with a high organic matter content.

Sulfadimethoxine and sulfaguanidine: their sorption potential on natural soils.

Sulfonamides (SAs) are one of the oldest groups of veterinary chemotherapeutic agents. As these compounds are not completely metabolized in animals, a high proportion of the native form is excreted in feces and urine. They are therefore released either directly to the environment in aquacultures and by grazing animals, or indirectly during the application of manure or slurry. Once released into the environment, SAs become distributed among various environmental compartments and may be transported to surface or ground waters. The physicochemical properties of SAs, dosage and nature of the matrix are the factors mainly responsible for their distribution in the natural environment. Although these rather polar compounds have been in use for over half a century, knowledge of their fate and behavior in soil ecosystems is still limited. Therefore, in this work we have determined the sorption potential of sulfadimethoxine and sulfaguanidine on various natural soils. The influence on sorption of external factors, such as ionic strength and pH, were also determined. The sorption coefficients (K(d)) obtained for the sulfonamides investigated were quite low (from 0.20 to 381.17 mL g(-1) for sulfadimethoxine and from 0.39 to 35.09 mL g(-1) for sulfaguanidine), which indicated that these substances are highly mobile and have the potential to run off into surface waters and/or infiltrate ground water. Moreover, the sorption of these pharmaceuticals was found to be influenced by OC, soil solution pH and ionic strength, with higher K(d) values for soils of higher OC and lower K(d) values with increasing pH and ionic strength.

Some sulfonamide drugs inhibit ATPase activity of heat shock protein 90: investigation by docking simulation and experimental validation.

Eight selected sulfonamide drugs were investigated as inhibitors of heat shock protein 90 (Hsp90). The investigation included simulated docking experiments to fit the selected compounds within the binding pocket of Hsp90. The selected molecules were found to readily fit within the ATP-binding pocket of Hsp90 in low-energy poses. The sulfonamides torsemide, sulfathiazole, and sulfadiazine were found to inhibit the ATPase activity of Hsp90 with IC(50) values of 1.0, 2.6, and 1.5 µM, respectively. Our results suggest that these well-established sulfonamides can be good leads for subsequent optimization into potent Hsp90 inhibitors.