Search

An efficient and facile synthesis of novel fluorinated imidazolium-tagged ionic liquids under microwave irradiation is described. Novel prepared ionic liquids was identified and confirmed by spectroscopic and elemental analysis. Synthesized ionic liquids (1-12) was explored for their antiproliferative inhibition potency against three selected human cancer cell lines (MCF-7, HepG-2 and CACO2). Screening results have revealed that some tested ionic liquids exhibited promising activity compared with standard drugs, especially compounds 5 and 6 which consistently produced low IC50 values. Preliminary structure activity relationship (SAR) studies have been performed to identify the relation between molecular structure and activity. in silico Analysis of ionic liquids was carried out based on ADME, Lipinski rule, drug likeness, toxicity profiles and other physico-chemical properties. All compounds were safe in toxicity profile and computed LD50 values were in accepted range (2.55-2.89 mol/kg). in silico Results have shown that Lipinski rule of five was in accept range, except compound 1 and 2.

A series of sixteen new ionic liquids (ILs) bearing imidazolium moiety were designed and synthesized under sustainable and green conditions which were confirmed by analytical and spectral techniques using 1H- & 13C-NMR, FT-IR, mass and elemental analysis. A panel of clinically isolated strains was used for in vitro inhibitory antimicrobial activities screening of synthesized ionic liquids. The results of antimicrobial assay showed that some of synthesized ionic liquids showed moderate to good activity. Among these ILs, ionic liquids 3, 4 and 5 (bearing alkyl chain with a phenyl group) significantly inhibited cell growth of strains. In this regard, these ionic liquids considered as promising antibacterial agents when compared with standard antibiotics. By encouraging in vitro antimicrobial screening, in silico ADMET evaluation has been performed and found excellent pharmacokinetic, bioavailability and toxicity profiles. Synthesized ionic liquids has found to be safe and non-toxic according to calculated in vivo computed LD50 values (2.49-2.80 mg/kg) for rat acute toxicity.

Plasmodium falciparum parasites causing cerebral malaria express specific PfEMP1 proteins (group A+CM) on infected erythrocytes. Group A+CM PfEMP1s allow entry into brain microvascular endothelial cells; this causes cell swelling and drives cerebral malaria pathology by disrupting the blood–brain barrier., Cerebral malaria (CM) is caused by the binding of Plasmodium falciparum–infected erythrocytes (IEs) to the brain microvasculature, leading to inflammation, vessel occlusion, and cerebral swelling. We have previously linked dual intercellular adhesion molecule-1 (ICAM-1)– and endothelial protein C receptor (EPCR)–binding P. falciparum parasites to these symptoms, but the mechanism driving the pathogenesis has not been identified. Here, we used a 3D spheroid model of the blood–brain barrier (BBB) to determine unexpected new features of IEs expressing the dual-receptor binding PfEMP1 parasite proteins. Analysis of multiple parasite lines shows that IEs are taken up by brain endothelial cells in an ICAM-1–dependent manner, resulting in breakdown of the BBB and swelling of the endothelial cells. Via ex vivo analysis of postmortem tissue samples from CM patients, we confirmed the presence of parasites within brain endothelial cells. Importantly, this discovery points to parasite ingress into the brain endothelium as a contributing factor to the pathology of human CM., Graphical Abstract

The discovery of a novel series of task-specific fluorinated pyridinium ionic liquids (TsILs) tagged with Schiff bases is reported using ultrasound-assisted and conventional syntheses. The synthesis required the quaternization of the appropriate pyridine Schiff base, followed by the metathesis of the resulting task-specific halogenated pyridinium ILs. The structures of the ILs were established by analytical and spectral data (IR, 1H NMR, 13C NMR, 19F NMR and mass spectrometry). In vitro antimicrobial activities of the synthesized ILs on both gram-positive (Bacillus cereus, Enterococcus faecalis, and Staphylococcus aureus) and gram-negative (Proteus mirabilis, Escherichia coli, and Pseudomonas aeruginosa) bacterial strains and two fungal strains (Candida albicans and Aspergillus brasiliensis) were evaluated. Ionic liquids 8, 18, 19 and 20 appear to be the most active antimicrobials among the synthesized series. Preliminary studies were carried out to understand the relationship between the molecular structures and the inhibition activities of the synthesized ILs. In addition, the results of in silico studies revealed that all compounds exhibited good pharmacokinetic, bioavailability and toxicity profiles. Furthermore, drug likeness analysis suggests that the synthesized ILs might have appropriate oral absorption and brain penetration for application. In vivo computed LD50 values (2.59–2.78 mol/kg) were calculated for rat acute toxicity, and the compounds were found to be non-toxic and in a safe range for further study.

Fused pyrimidines composed of alternating heteroatoms and a pyrimidine moiety were synthesized efficiently using readily available starting material 4-hydroxycoumarin, aromatic aldehydes, and urea/thiourea at room temperature. Acid, metal salts, and surfactants were screened for their influence on catalytic activity in three-component reactions and sodium lauryl sulphate (SLS) was used as the best catalyst with different concentrations. Screening results of catalyst loading from our investigation showed that good to excellent yields were obtained with 10 mol%. Our method efficiently synthesized heterocycles and avoided the use of hazardous solvents and conventional organic solvents. Our procedure which involves a surfactant is operationally simple, environmentally benign, has excellent yields, short reaction times, and synthetically is as efficient as conventional procedures using organic solvents.

Synthesis of Cu-Al hydrotalcite by co precipitation method is being described. Synthesized nano catalyst has been characterized by powder X-ray diffraction, scanning electron microscopy, FT-IR and thermogravimetric analyses which confirm hydrotalcite-like structure. Effect of molar concentration, catalyst loading, reaction time and catalytic activity have been investigated in the synthesis of benzoxazoles under solvent free conditions using 2-amino phenol and benzoyl chloride. The influence of the hydrotalcite and their different amounts on reactivity was studied. Catalyst can be recycle and used for further reaction without losing its activity.

Malaria is a highly inflammatory disease caused by Plasmodium infection of host erythrocytes. However, the parasite does not induce inflammatory cytokine responses in macrophages in vitro and the source of inflammation in patients remains unclear. Here, we identify oxidative stress, which is common in malaria, as an effective trigger of the inflammatory activation of macrophages. We observed that extracellular reactive oxygen species (ROS) produced by xanthine oxidase (XO), an enzyme upregulated during malaria, induce a strong inflammatory cytokine response in primary human monocyte‐derived macrophages. In malaria patients, elevated plasma XO activity correlates with high levels of inflammatory cytokines and with the development of cerebral malaria. We found that incubation of macrophages with plasma from these patients can induce a XO‐dependent inflammatory cytokine response, identifying a host factor as a trigger for inflammation in malaria. XO‐produced ROS also increase the synthesis of pro‐IL‐1β, while the parasite activates caspase‐1, providing the two necessary signals for the activation of the NLRP3 inflammasome. We propose that XO‐produced ROS are a key factor for the trigger of inflammation during malaria.

A facile, efficient, and convenient synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives is described using aromatic aldehydes, ethyl acetoacetate, and 2-amino benzothiazole in the presence of l-proline under solvent-free conditions. Present methodology has advantages such as short reaction time, no side products, and easy to work up. Synthesized library compounds have been evaluated for their antitumor and antimicrobial activity. Further, we have compared the experimental work with theoretical parameters using molecular property analysis to develop new ideas about the preparation of pyrimido benzothiazole derivatives for their possible application against cancer and chronic microbial diseases. It has been concluded that Petra/osiris/molinspiration (POM) analyses might prove to be a suitable method to correlate the structural features of 4H-pyrimido[2,1-b]benzothiazole derivatives with their promising combined antimicrobial/antitumor activity and may contribute to the development of novel antimicrobial and antitumor agents against drug resistance.

One-pot condensation of 4-hydroxy coumarins, aldehydes and urea/thiourea to build C–C and C–N bonds is described. Fused pyrimidines have been synthesized under mild reaction conditions using L-proline. The protocol has been performed rapidly and efficiently in water under metal free conditions. Heterocyclic derivatives have been synthesized using the present methodology and avoid the use of hazardous solvents over conventional organic solvents. A proposed mechanism could be established for three component reactions. The present study reveals the first case in which L-proline has been explored as a homogeneous catalyst in the synthesis of fused pyrimidines in water under microwave irradiation. This synthesis involves simple workup and acceptable efficiency. The most notable feature of this protocol is the ability of the catalyst to influence asymmetric induction in the reaction.

Series of curcumin derivatives/analogues were designed and efficient method for synthesis thereof is described. All the synthesized compounds have been screened for their cytotoxicity and evaluated their antioxidant activity. Cytotoxicity effect has been evaluated against three cell lines Hep-G2, HCT-116 and QG-56 by MTT assay method. Structure activity relationship has revealed that particularly, compound 3c, (IC50 value 6.25 μM) has shown better cytotoxicity effect against three cell lines. According to results of SAR study, it was found that 4H-pyrimido[2,1-b]benzothiazole derivatives (2e and 2f), pyrazoles (3a, 3b, 3c and 3d) benzylidenes (4d) exhibited better antioxidant activity than curcumin. A correlation of structure and activities relationship of these compounds with respect to drug score profiles and other physico-chemical properties of drugs are described and verified experimentally.

Novel KOH-loaded MgO and hydrotalcite as basic catalysts have been synthesized and were characterized by XRD, SEM and their basicity. The effect of the KOH wt%, reaction time, basicity and catalyst loading have been investigated in three-component reactions of aldehydes, 2-amino benzothiazole and 2-naphthol. The present studies showed the impact of KOH loading and reaction time. The best conversion and yield at 70 °C obtained were 93% and 88%, respectively. Hydrotalcite could be reused four times without a loss of the catalytic efficiency. Present catalytic system requires a short reaction time, is non toxic, easy to workup, has a good catalytic activity and gives a high efficiency.

An efficient and simple protocol is described for synthesis of coumarin derivatives using Mg–Al-CO 3 and Ca–Al-CO 3 hydrotalcite as an environmental friendly and reusable heterogeneous catalyst under solvent free conditions. The catalysts were characterized by Hammett titration, SEM and XRD data. Present study revealed that catalytic activity and basicity depend on compositions of hydrotalcite. The calcined hydrotalcite with an Mg/Al of 3:1 derived from calcinations at 750 K was found to be suitable catalyst that gives the highest basicity and the best catalytic activity for this reaction. Catalyst allows short reaction time, high catalytic activity, easy to work up and is reusable. Step economy, atom efficiency and solvent free conditions are some important salient features of this protocol.

A series of sixteen curcumin derivatives (CURC-D) were designed and evaluated for their antibacterial/antifungal activity. POM analyses showed that lipophilicity and presence of (X–Y) pharmacophore site (X, Y = O, N) are the major factors that governed the orientation in determining antibacterial and/antifungal activity. Furthermore, it was also found that some of the POM analyzed CURC-derivatives have a closed pharmacophore sites which might be responsible of low bioactivity. To confirm the electronic, steric, and hydrophobic requirements for future modifications, we have also carried out receptor-based electrostatic analysis. Therefore, we conclude that POM analyses may prove to be a suitable method to correlate structural features of CURC-D with their promising combined antibacterial/antifungal activity and may contribute to the development of novel antimicrobial agents against drug-resistant human pathogens.

An efficient method is described for the synthesis of 2-aminobenzothiazolomethyl naphthol derivatives by one-pot three-component reaction of aldehydes, 2-naphthol, and 2-amino benzothiazole using triton X-100 as a catalyst in water with good yield. The synthesized compounds have been characterized by IR, 1H NMR, 13C NMR, and mass spectra. The synthesized compounds were screened for their antibacterial activity against gram-positive and gram-negative bacteria viz. Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhi, Escherichia coli, Bacillus cereus, and Providencia rettegeri and fungal activity against fungal strain such as Aspergillus niger, Aspergillus fumigatus, and Aspergillus flavus. Synthesized compounds exhibited MICs value between 3.25 and 12.5 μg/mL against bacterial strains and 6.25 and 12.5 μg/mL against fungal strains as shown in Tables 4 and 5, respectively. Derivatives 5c and 5h were equipotent activity as ciprofloxacin against E. coli and 5k against P. aeruginosa and B. cereus. Derivatives 5e, 5g, and 5k exhibited excellent antifungal activity against all tested fungal strains. Ciprofloxacin and fluconazole have been used as standard drugs for antibacterial and antifungal activity, respectively.

An efficient method has been developed for the preparation of 4H-pyrimido[2,1-b]benzothiazole derivatives by the condensation of aldehydes, β-ketoester, and 2-amino benzothiazole under solvent and solvent-free conditions using various catalysts. The reaction uses benzothiazole as a new component, and good yield is obtained at 60–65°C under solvent-free conditions. Atom economies, good yield, environmentally benign, and easy to work-up are some of the important features of this protocol. The present study suggests that acetic acid and metal catalysts follow different mechanism. In acetic acid, 2-amino benzothiazole reacts with benzaldehyde, and resultant intermediate reacts with ethyl acetoacetate to give final product, whereas in the presence of metal catalysts, 2-amino benzothiazole first reacts with ethyl acetoacetate, and resultant intermediate reacts with benzaldehyde to give pyrimido[2,1-b]benzothiazole.

A novel, one-pot, simple, efficient procedure for 4H-pyrimido[2,1-b]benzothiazole (4a-h), pyrazole (6a-d) and benzylidene (7a-d) derivatives of curcumin under solvent and solvent free conditions in microwave with good yield is have been synthesized. The synthesized compounds were evaluated for their antibacterial activity against gram-positive and gram-negative bacteria viz. Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhi, Escherichia coli, Bacillus cereus and Providencia rettgeri and antifungal activity against fungi viz Aspergillus niger, Aspergillus fumigates, Aspergillus flavus. Detailed mechanistic study shows reaction proceeds through Knoevenagel type intermediate 3a which has been suggested as key intermediate for reaction (Fig. 3).

Aluminum trichloride acts as readily available, inexpensive, and efficient catalyst for one-pot three-component condensation reaction of aldehydes, dicarbonyl, and 2-amino benzothiazole under the solvent-free conditions to afford the 4H-pyrimido[2,1-b][1,3]benzothiazole derivatives 4 with good yield. The compounds synthesized in this study were evaluated for their antibacterial activities against gram-positive and gram-negative bacteria, viz., Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhi, Escherichia coli, Bacillus cereus, and Providencia rettegeri. Compounds 4c, 4d, 4f, 4g, and 4h showed their good activities against tested bacterial species. Pyrimidine derivatives 4d, 4f, and 4g have shown good antifungal activities against tested fungal strains, such as Aspergillus niger, Aspergillus fumigates, Aspergillus flavus, etc.

A convenient, facile, and efficient synthesis of different nitrogen containing heterocycles is reported.

An efficient method has been developed for the preparation of 4H-pyrimido[2,1-b]benzothiazole derivatives by the condensation of aldehydes, β-ketoester, and 2-amino benzothiazole under solvent and solvent-free conditions using various catalysts. The reaction uses benzothiazole as a new component, and good yield is obtained at 60–65°C under solvent-free conditions. Atom economies, good yield, environmentally benign, and easy to work-up are some of the important features of this protocol. The present study suggests that acetic acid and metal catalysts follow different mechanism. In acetic acid, 2-amino benzothiazole reacts with benzaldehyde, and resultant intermediate reacts with ethyl acetoacetate to give final product, whereas in the presence of metal catalysts, 2-amino benzothiazole first reacts with ethyl acetoacetate, and resultant intermediate reacts with benzaldehyde to give pyrimido[2,1-b]benzothiazole.

Release of extracellular DNA (eDNA) was observed duringin vitrogrowth of a clinical strain ofAcinetobacter baumannii. Membrane vesicles (MV) of varying diameter (20–200 nm) containing DNA were found to be released by transmission electron microscopy (TEM) and atomic force microscopy (AFM). An assessment of the characteristics of the eDNA with respect to size, digestion pattern by DNase I/restriction enzymes, and PCR-sequencing, indicates a high similarity with genomic DNA. Role of eDNA in static biofilm formed on polystyrene surface was evaluated by biofilm augmentation assay using eDNA available in different preparations, for example, whole cell lysate, cell-free supernatant, MV suspension, and purified eDNA. Biofilm augmentation was seen up to 224.64%, whereas biofilm inhibition was 59.41% after DNase I treatment: confirming that eDNA facilitates biofilm formation inA. baumannii. This is the first paper elucidating the characteristics and role of eDNA inA. baumanniibiofilm, which may provide new insights into its pathogenesis.

A new green protocol for the efficient surfactant catalyzed synthesis of 2-aminobenzothiazolomethyl naphthols and 5-(2-aminobenzothiazolomethyl)-6-hydroxyquinolines from substituted aromatic aldehydes, 2-aminobenzothiazole and 2-naphthol or 6-hydroxyquinoline at room temperature in water was developed for the first time. The influence of the sodium lauryl sulphate (SLS) micelles and their different concentrations on reactivity of 2-aminobenzothiazolomethyl naphthol was studied. It was found that best yield was obtained with 10 mol% catalyst loading with minimum time as compared to when other surfactants and catalysts were used. The best yield of product was achieved by using 10 mol% of SLS. This procedure resulted in a general and environmentally benign protocol and has the advantages of better reusability of the catalyst system, excellent yield, short reaction time and ease of work up.

A kaolin catalyzed solvent-free synthesis for new heterocyclic compounds is described. A series of heterocyclic compounds can be readily obtained using the three-component reaction of diketones, aldehydes and 2-amino benzothiazole, urea or thiourea. The mechanism of the three component kaolin catalyzed Biginelli (using urea and thiourea) and Biginelli like (using 2-amino benzothiazole) reaction has been investigated. This is the first time that we have isolated and characterized the key intermediates using 1H NMR, 13C NMR and ESI-mass spectral characterization. Imine 3 and Knoevenagel type intermediate 4 were strongly suggested as key intermediates by mechanistic study. The reaction is simple, clean and good yield is obtained within minutes.

A simple, efficient and step-economy synthesis to afford the library of 4H-pyrimido[2,1-b][1,3]benzothiazole derivatives of curcumin (4a–4h) from readily available substrates curcumin (potential biological molecule), 2-amino benzothiazole (biological active) and substituted aromatic aldehydes using novel heterogeneous calcined Mg-Al-CO3 hydrotalcite under solvent free conditions is described. The calcined hydrotalcite with an Mg/Al ratio of 3:1 derived from calcinations at 750 K was found to be a suitable catalyst that gives the highest basicity and the best catalytic activity for this reaction. The catalysts were characterized with XRD and SEM and Hammett titration method. This protocol has several advantages such as easy to work up, high activity of catalyst and reusability.

The synthesis of the 4H-pyrimido[2,1-b][1,3]benzothiazole (1a–1h), 1,2,4-triazoloquinazolines (2a,2b), octahydroquinazolinones (3a,3b) and fused thiazolo[2,3-b]quinazolinone (4a,4b) by multicomponent reactions using aldehydes, dicarbonyl and 2-amino benzothiazole/3-amino-1,2,4-triazole/urea/thiorea has been carried out in the presence of Mg–Al–CO3 and Ca–Al–CO3 hydrotalcite as a heterogeneous catalyst. Hydrotalcites need short reaction times, are non-toxic, easy to work up and reusable under solvent free conditions, hence making this process environment friendly. A detailed mechanistic study shows that the reaction using urea proceeds through imine intermediate 6. In addition, we have isolated and characterized the key intermediate of the reaction by using hydrotalcite.