Evaluation of antibacterial, cytotoxicity, and apoptosis activity of novel chromene-sulfonamide hybrids synthesized under solvent-free conditions and 3D-QSAR modeling studies.

In this study, eleven novel chromene sulfonamide hybrids were synthesized by a convenient method in accordance with green chemistry. At first, chromene derivatives (1-9a) were prepared through the multi-component reaction between aryl aldehydes, malononitrile, and 3-aminophenol. Then, synthesized chromenes were reacted with appropriate sulfonyl chlorides by grinding method to give the corresponding chromene sulfonamide hybrids (1-11b). Synthesized hybrids were obtained in good to high yield and characterized by IR, 1HNMR, 13CNMR, CHN and melting point techniques. In addition, the broth microdilution assay was used to determine the minimal inhibitory concentration of newly synthesized chromene-sulfonamide hybrids. The MTT test was used to determine the cytotoxicity and apoptotic activity of the newly synthesized compounds against fibroblast L929 cells. The 3D­QSAR analysis confirmed the experimental assays, demonstrating that our predictive model is useful for developing new antibacterial inhibitors. Consequently, molecular docking studies were performed to validate the findings of the 3D-QSAR analysis, confirming the potential binding interactions of the synthesized chromene-sulfonamide hybrids with the target enzymes. Molecular docking studies were employed to support the 3D-QSAR predictions, providing insights into the binding interactions between the newly synthesized chromene-sulfonamide hybrids and their target bacterial enzymes, thereby reinforcing the potential efficacy of these compounds as antibacterial agents. Also, some of the experimental outcomes supported or conflicted with the pharmacokinetic prediction (especially about compound carcinogenicity). The performance of ADMET predictor results was assessed. The work presented here proposes a computationally driven strategy for designing and discovering a new sulfonamide scaffold for bacterial inhibition.

A Comprehensive Review on the Boosted Effects of Anion Vacancy in the Heterogeneous Photocatalytic Degradation, Part II: Focus on Oxygen Vacancy.

Environmental problems, including the increasingly polluted water and the energy crisis, have led to a need to propose novel strategies/methodologies to contribute to sustainable progress and enhance human well-being. For these goals, heterogeneous semiconducting-based photocatalysis is introduced as a green, eco-friendly, cost-effective, and effective strategy. The introduction of anion vacancies in semiconductors has been well-known as an effective strategy for considerably enhancing the photocatalytic activity of such photocatalytic systems, giving them the advantages of promoting light harvesting, facilitating photogenerated electron-hole pair separation, optimizing the electronic structure, and enhancing the yield of reactive radicals. This Review will introduce the effects of anion vacancy-dominated photodegradation systems. Then, their mechanism will illustrate how an anion vacancy changes the photodegradation pathway to enhance the degradation efficiency toward pollutants and the overall photocatalytic performance. Specifically, the vacancy defect types and the methods of tailoring vacancies will be briefly illustrated, and this part of the Review will focus on the oxygen vacancy (OV) and its recent advances. The challenges and development issues for engineered vacancy defects in photocatalysts will also be discussed for practical applications and to provide a promising research direction. Finally, some prospects for this emerging field will be proposed and suggested. All permission numbers for adopted figures from the literature are summarized in a separate file for the Editor.

A comprehensive review on the boosted effects of anion vacancy in the heterogeneous photocatalytic degradation, part I: Focus on sulfur, nitrogen, carbon, and halogen vacancies.

The greenest environmental remediation way is the photocatalytic degradation of organic pollutants. However, limited photocatalytic applications are due to poor sunlight absorption and photogenerated charge carriers' recombination. These limitations can be overcome by introducing anion vacancy (AV) (O, S, N, C, and Halogen) defects in semiconductors that enhance light harvesting, facilitate charge separation, modulate electronic structure, and produce reactive radicals. In continuing part A of this review, in this part, we summarized the recent AVs' research, including S, N, C, and halogen vacancies on the boosted photocatalytic features of semiconductor materials, like metal oxides/sulfides, oxyhalides, and nitrides in detail. Also, we outline the recently developed AV designs for the photocatalytic degradation of organic pollutants. The AV creating and analysis methods and the recent photocatalytic applications and mechanisms of AV-mediated photocatalysts are reviewed. AV engineering photocatalysts' challenges and development prospects are illustrated to get a promising research direction.

A Z-scheme CdS/Ag3PO4 catalyst: Characterization, experimental design and mechanism consideration for methylene blue.

Due to the explosive use of Azo dyes in various industries such as textiles, discharging these industrial effluents into the environment critically polluted water supplies. Accordingly, constructing/developing novel binary catalysts to diminish the pollution extent of such effluents before discharging into environment is an excellent issue in environmental chemistry. Here, a binary CdS/ Ag3PO4 was constructed, and its boosted photocatalytic activity was proven against methylene blue (MB), as a model dye pollutant. The Wurtzite CdS and Ag3PO4 cubic crystal nanoparticles were synthesized and coupled mechanically. The binary sample's lowest photoluminescence (PL) results confirm a higher e/h separation. DRS results confirmed a decreased energy gap for the coupled system. The semiconductors' VB and CV potentials were calculated and used for constructing of Z-scheme mechanism. The photocatalytic activity was followed via an experimental design approach. The model F-value of 89.75 > F0.05,14,13 = 2.42 and LOF F-value of 6.57 < F0.05,10, 3 = 8.79 reveal that the model well processed data. The optimal run conditions were CMB: 5 ppm, Catalyst dose: 1 g/L, pH: 3.25, and irradiation time: 139 min, at which 85% of MB molecules were degraded. Based on the trend of ascorbic acid > isopropanol > formic acid ≈ nitrate obtained for the scavengers' importance in decreasing the photocatalyst activity, superoxide radicals had the highest effect in MB degradation and then •OH. The results showed the direct Z-scheme has the main effect on MB degradation by the binary sample.

Recent Advances in Biological Active Sulfonamide based Hybrid Compounds Part C: Multicomponent Sulfonamide Hybrids.

Sulfonamides, with the general formula R-SO2NR1R2, have attracted great attention since the early discovery of sulfonamide-containing antibacterial drugs. The combinations of certain sulfonamides and other drug molecules to form sulfonamide hybrids are being used to develop novel formulations with greater effectiveness and in a huge range of therapeutic applications such as antimicrobial, antifungal, anti-inflammatory, antitubercular, antiviral, antidiabetic, antiproliferative, carbonic anhydrase inhibitor, antimalarial, anticancer and other medicinal agents. Part C of this review presents recent advances in designing and developing multicomponent sulfonamide hybrids containing more than one biologically active heterocycle, such as coumarin, indole, pyridine, pyrimidine, pyrazole, triazole, oxazole, oxadiazole, triazine, quinazoline, and thiadiazol. This review aims to highlight the status of the hybridization technique in synthesizing biological and computational studies of novel sulfonamide hybrids that were designed and presented between 2016 and 2020.

Recent Advances in Biological Active Sulfonamide based Hybrid Compounds Part B: Two-Component Sulfonamide Hybrids.

Sulfonamide compounds, also known as sulfa drugs, are a significant class of synthetic bacteriostatic antimicrobials and were the primary source of therapy against bacterial infections before the introduction of penicillin in 1941. Hybridization of sulfonamides with various pharmaceutically active heterocyclic moieties leads to sulfonamide hybrids with a wide variety of biological activities. Part B of this review presents the most recent advances in designing and developing more two-component sulfonamide hybrids containing triazole, thiadiazole, triazine, oxazole/ benzoxazole, isoxazole, oxadiazole, imidazole, benzimidazole, furan, benzofuran, thiophene, pyrrole, indazole, tetrazole, chromene/ chromone, pyridazine, quinoxaline, acridine, phthalazine, and xanthone between 2015 and 2020. We hope this review helps the scientific community in designing more useful sulfonamide hybrid drugs.

Recent Advances in Biological Active Sulfonamide based Hybrid Compounds Part A: Two-Component Sulfonamide Hybrids.

Sulfonamides constitute an important class of drugs, with many types of pharmacological agents possessing antibacterial, anti-carbonic anhydrase, anti-obesity, diuretic, hypoglycemic, antithyroid, antitumor, and anti-neuropathic pain activities. The sulfonamides are the compounds that have general formula R-SO2NHR', where the functional group is bound to aromatic, heterocycle, and aliphatic groups. The nature of the R and R' moiety is variable, starting with hydrogen and ranging to a variety of moieties incorporating organic compounds such as coumarin, isoxazole, tetrazole, pyrazole, pyrrole, and so many other pharmaceutical active scaffolds that lead to a considerable range of hybrids named as sulfonamide hybrids. Part A of this review presents the most recent advances in designing and developing two-component sulfonamide hybrids containing coumarin, indole, quinoline, isoquinoline, chalcone, pyrazole/pyrazoline, quinazoline, pyrimidine, thiazole, benzothiazole, and pyridine between 2015 and 2020. Specifically, the authors review the scientific reports on the synthesis and biological activity of this kind of hybrid agent.

Targeting and ultrabroad insight into molecular basis of Resistance-nodulation-cell division efflux pumps.

Resistance-nodulation-cell devision (RND) efflux pump variants have attracted a great deal of attention for efflux of many antibiotic classes, which leads to multidrug-resistant bacteria. The present study aimed to discover the interaction between the RND efflux pumps and antibiotics, find the conserved and hot spot residues, and use this information to target the most frequent RND efflux pumps. Protein sequence and 3D conformational alignments, pharmacophore modeling, molecular docking, and molecular dynamics simulation were used in the first level for discovering the function of the residues in interaction with antibiotics. In the second level, pharmacophore-based screening, structural-based screening, multistep docking, GRID MIF, pharmacokinetic modeling, fragment molecular orbital, and MD simulation were utilized alongside the former level information to find the most proper inhibitors. Five conserved residues, containing Ala209, Tyr404, Leu415, Asp416, and Ala417, as well as their counterparts in other OMPs were evaluated as the crucial conserved residues. MD simulation confirmed that a number of these residues had a key role in the performance of the efflux antibiotics; therefore, some of them were hot spot residues. Fourteen ligands were selected, four of which interacted with all the crucial conserved residues. NPC100251 was the fittest OMP inhibitor after pharmacokinetic computations. The second-level MD simulation and FMO supported the efficacy of the NPC100251. It was exhibited that perhaps OMPs worked as the intelligent and programable protein. NPC100251 was the strongest OMPs inhibitor, and may be a potential therapeutic candidate for MDR infections.

A designed experiment for CdS-AgBr photocatalyst toward methylene blue.

A boosted photocatalytic activity was observed for the CdS-AgBr nanocomposite in the degradation of methylene blue (MB). The experimental design method based on the response surface methodology (RSM) approach used to study the simultaneous interaction effects between the influencing variables. Analysis of variance (ANOVA) of the results confirmed a significant model for processing the data because an F value of 32.34 for the suggested model was higher than that of the critical value of F0.05, 14, 13 = 2.55 at 95% confidence interval. This analysis also showed a non-significant lack of fit (LOF) (as a measure of the randomness of the deviations around the obtained data) because the LOF F value of 8.27 was smaller than that of the critical value of F0.05, 10, 3 = 8.79. R2 values near to unity were achieved (the multiple correlation coefficients R2 (R2 = 0.9627), adjusted R2 (adj-R2 = 0.9226), and predicted R2 (pred-R2 = 0.7423)). Six center points suggested by the model included the following conditions: pH, 6.1; CMB, 3.5 mg/L; a dose of the catalyst, 0.68 g/L; and irradiation time, 40.5 min. During the center point runs, the degradation efficiencies were obtained in the range of 38 to 43%. The optimal run included pH, 9; catalyst dosage, 1 g/L; irradiation time, 60 min; and CMB, 2 mg/L, and the best removal efficiency of 98% was achieved during these conditions.

Synthesis of some novel coumarin isoxazol sulfonamide hybrid compounds, 3D-QSAR studies, and antibacterial evaluation.

With the progressive and ever-increasing antibacterial resistance pathway, the need for novel antibiotic design becomes critical. Sulfonamides are one of the more effective antibiotics against bacteria. In this work, several novel sulfonamide hybrids including coumarin and isoxazole group were synthesized in five steps starting from coumarin-3-carboxylic acid and 3-amino-5-methyl isoxazole and assayed for antibacterial activity. The samples were obtained in good to high yield and characterized by FT-IR, 13C-NMR, 1H-NMR, CHN and melting point techniques. 3D-QSAR is a fast, easy, cost-effective, and high throughput screening method to predict the effect of the compound's efficacy, which notably decreases the needed price for experimental drug assay. The 3D-QSAR model displayed acceptable predictive and descriptive capability to find r2 and q2 the pMIC of the designed compound. Key descriptors, which robustly depend on antibacterial activity, perhaps were explained by this method. According to this model, among the synthesized sulfonamide hybrids, 9b and 9f had the highest effect on the gram-negative and gram-positive bacteria based on the pMIC. The 3D-QSAR results were confirmed in the experimental assays, demonstrating that our model is useful for developing new antibacterial agents. The work proposes a computationally-driven strategy for designing and discovering new sulfonamide scaffold for bacterial inhibition.

Synthesis and Anticancer Activity Assay of Novel Chalcone-Sulfonamide Derivatives.

Today Cancer remains to be one of the most deadly diseases in the world. Due to the potential anticancer activity of the chalcone and sulfonamide moieties, five novel hybrid compounds containing both structures have been designed and synthesized in 3 steps. The synthesized compounds were established on the basis of IR, 1H NMR, 13C NMR spectral data, and elemental analysis and also they were screened for in-vitro anticancer activity on human breast cancer cell line MCF-7. Among them, (E)-2-methoxy-N-(4-methoxyphenyl)-5-(3-(4-nitrophenyl) acryloyl) benzene sulfonamide (4) showed the most potent anticancer activity against MCF-7 cell line.

ZSM-5-SO3H: An Efficient Catalyst for Acylation of Sulfonamides Amines, Alcohols, and Phenols under Solvent-Free Conditions.

Sulfonamides amines, alcohols, and phenols were efficiently acylated with carboxylic acid anhydrides and chlorides using ZSM-5-SO3H as catalyst under mild and solvent-free conditions. Also, direct esterification of alcohols with carboxylic acids occurred readily in the presence of this catalyst. Different types of amides and esters were obtained in moderate to high yields and purity after a simple workup. No chromatographic separation is needed for isolation of the acylated product. The catalyst was recovered and reused for up to four times without a noticeable decrease in catalytic activity.

In situ trapping of Boc-2-pyrrolidinylmethylzinc iodide with aryl iodides: direct synthesis of 2-benzylpyrrolidines.

Addition of (S)-(+)-tert-butyl 2-(iodomethyl)pyrrolidine-1-carboxylate to activated zinc, aryl halides, and a catalyst derived from Pd(2)(dba)(3) (2.5 mol %) and SPhos (5 mol %) in DMF allows trapping of the corresponding organozinc reagent, with formation of Boc-protected 2-benzylpyrrolidines (20-72%).

Synthesis, in vitro antibacterial and carbonic anhydrase II inhibitory activities of N-acylsulfonamides using silica sulfuric acid as an efficient catalyst under both solvent-free and heterogeneous conditions.

Silica sulfuric acid catalyzes efficiently the reaction of sulfonamides with both carboxylic acid anhydrides and chlorides under solvent-free and heterogeneous conditions. All the reactions were done at room temperature and the N-acylsulfonamides were obtained with high yields and purity via an easy work-up procedure. This method is attractive and is in a close agreement with green chemistry. These compounds were also investigated for antibacterial activity, including Gram-positive cocci and Gram-negative bacilli, and carbonic anhydrase II inhibitory activity.

Uranyl-selective PVC membrane electrodes based on some recently synthesized benzo-substituted macrocyclic diamides.

Four different recently synthesized macrocyclic diamides were studied to characterize their abilities as uranyl ion carriers in PVC membrane electrodes. The electrodes based on macrocycle 1,18-diaza-3,4;15,16-dibenzo-5,8,11,14,21,24-hexaoxacyclohexaeicosane-2,17-dione resulted in a Nernstian response for UO(2)(2+) ion over wide concentration ranges. The linear concentration range for the polymeric membrane electrode (PME) is 3.0x10(-6)-8.2x10(-3) M with a detection limit of 2.2x10(-6) and that for the coated graphite electrode (CGE) is 5.0x10(-7)-1.5x10(-3) M with a detection limit of 3.5x10(-7) M. The electrodes manifest advantages of low resistance, very fast response and, most importantly, good selectivities relative to a wide variety of other cations.