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Uropathogenic Escherichia coli (UPEC) accounts for the majority of complicated and uncomplicated urinary tract infections. The use of phytomolecules in the treatment of UTI is fast gaining attention. The current report identifies a multidrug-resistant strain (QSLUPEC7), which is a strong biofilm producer, among the considered clinical isolates. The antimicrobial and antibiofilm activity was evaluated for the phytomolecule, Type A procyanidin (TAP) from Cinnamomum zeylanicum against QSLUPEC7. TAP treatment did not affect the growth of the MDR strain but affected the biofilm formation (~70% inhibition). The confocal microscopic examination reveals the biofilm inhibition and the live cells in the biofilm corroborates the antimicrobial results. Further, the synergy studies of TAP and nitrofurantoin (NIT) were carried out at different pH. TAP acts synergistically with nitrofurantoin at different pH considered. A closer look in the results reveals that at pH 5.8, maximum growth inhibition is recorded. The gene expression analysis shows that TAP alone and in combination with NIT downregulates the major fimbriae adhesins of UPEC. The results conclude that the TAP has an antibiofilm activity against the multidrug-resistant strain of UPEC, without affecting the growth. Also, TAP reciprocally cooperates with nitrofurantoin at different pH by downregulating the adhesins of UPEC.

The high mortality rate and the increasing prevalence of Mtb resistance are the major concerns for the Tuberculosis (TB) treatment in this century. To counteract the prevalence of Mtb resistance, we have synthesized 2-aryl benzazole based dual targeted molecules. Compound 9m and 9n were found to be equally active against replicating and non-replicating form of Mtb (MIC(MABA) 1.98 and 1.66 μg/ml; MIC(LORA) 2.06 and 1.59 μg/ml respectively). They arrested the cell division (replicating Mtb) by inhibiting the GTPase activity of FtsZ with IC50 values 45 and 64 μM respectively. They were also capable of kill Mtb in non-replicating form by inhibiting the biosynthesis of menaquinone which was substantiated by the MenG inhibition (IC50 = 11.62 and 7.49 μM respectively) followed by the Vit-K2 rescue study and ATP production assay.

Four new aromatic diimide–diol monomers were synthesized from bisphenol A dianhydride and hydroxyamines. The poly(ether–imide)s (PEI-1 to PEI-4) were synthesized from these diols and 4,4′-difluorobenzophenone-IV via carbonyl-activated aromatic nucleophilic fluoro displacement reaction. The chemical structures of the monomers and PEIs were confirmed by Fourier transform infrared spectrometer and proton nuclear magnetic resonance spectroscopies. The PEIs synthesized here were amorphous and soluble in polar aprotic solvents and low-boiling organic solvents. The PEIs had good thermal stability, 10% weight loss occurred in the temperatures range of 400–448°C, and char yields at 800°C under nitrogen atmosphere was in the range of 14–22%. The limiting oxygen index values of PEIs were in the range of 23.1–26.3, and such PEIs can be used as self-extinguishing polymers. The dielectric constants of the PEIs were in the range of 3.30–4.00, and such PEIs can be used as electrical insulation materials for systems operating at high temperature for long time.

The synthesis of strong electron-withdrawing group substituted aromatic amine and phenol-based benzoxazines is hampered due to the poor solubility of the reactant. In this article, a simple methodology is presented to synthesize the strong electron-withdrawing groups substituted benzoxazine monomers from a solution method using a low-boiling polar solvent. In order to achieve this, we used formaldehyde as a reactant as well as a solvent, and the reaction was carried out for a longer time. Also, benzylaniline derivatives were successfully prepared through benzoxazine. The monomers were polymerized by using solution polymerization method using lithium bromide as a catalyst. The structure of the monomers and polymers was confirmed by Fourier transform infrared and nuclear magnetic resonance spectroscopy. The thermally activated polymerization of the monomers was evaluated by differential scanning calorimetry, and thermal properties of polymers were analyzed by thermogravimetric analysis.

Designing small molecular prototypes having potential to disrupt binding interfaces of pro-apoptotic–anti-apoptotic/BH3-only proteins is a promising strategy in cancer chemotherapy. Several natural and synthetic chemical compounds have been reported as inhibitors or BH3-mimetics to anti-apoptotic proteins of the Bcl-2 family playing essential roles in apoptosis. In the present study, chemical synthesis, structural characterizations and anti-cancer effect of 2-hydroxy-3,5-dinitrobenzamide (HDNB), a chemical compound identified on the basis of pharmacophoric features of hBaxBH3 peptide have been systematically reported. The chemopreventive effect of the HDNB was assessed on N-nitroso-N-methylurea-induced Wistar female rats of mammary gland carcinogenesis for the study period of 18 weeks. The carcinogenesis Wistar rats were subjected to oral administration of a low-dose (8 mg kg−1 b.w.), medium-dose (40 mg kg−1 b.w.) and high-dose (200 mg kg−1 b.w.) of the HDNB in three different experimental setups. Strikingly, a medium-dose (40 mg kg−1 b.w.) of the HDNB showed appreciable potential to reverse the abnormalities of various biochemical parameters in blood samples and as well in breast tissues to the values close to that of healthy control or to that of the standard (tamoxifen) control. The chemopreventive potential of the HDNB could be chiefly attributed to its ability to restore antioxidants and as well apoptosis inducing properties in Wistar animal models.

The high mortality rate and increasing prevalence of resistant Mtb are the major concerns for the Tuberculosis (TB) treatment in this century. To curtail the prevalence of resistant Mtb, we have prepared 1,3-oxazine-2-one based dual targeted molecules. Compound 67 and 68 were found to be equally active against replicating and non-replicatiing form of Mtb (MICMABA 3.48 and 2.97 μg/ml; MICLORA 2.94 and 2.15 μg/ml respectively). They had found to suppress the biosynthesis of alfa, methoxy and keto-mycolate completely, as well as inhibit enzymatic activity of MenG (IC50 = 9.11 and 6.25 μg/ml respectively for H37Ra; IC50 = 11.76 and 10.88 μg/ml respectively for M smegmatis).

Background:The available treatment option for any type of cancer including CTCL is chemotherapy and radiation therapy which indiscriminately persuade on the normal cells. One way out for selective destruction of CTCL cells without damaging normal cells is the use of histone deacetylase inhibitors (HDACi). Despite promising results in the treatment of CTCL, these HDACi have shown a broadband inhibition profile, moderately selective for one HDAC class but not for a particular isotype. The prevalence of drug-induced side effects leaves open a narrow window of speculation that the decreased therapeutic efficacy and observed side effects may be most likely due to non specific HDAC isoform inhibition. The aim of this paper is to synthesis and evaluates HDAC8 isoform specific inhibitors.Methods:Based on the preliminary report on the design and in silico studies of 52 hydroxamic acid derivatives bearing multi-substituent heteroaromatic rings with chiral amine linker, five compounds were shortlisted and synthesized by microwave assisted approach and high yielding synthetic protocol. A series of in vitro assays in addition to HDAC8 inhibitory activity was used to evaluate the synthesised compounds.Results:Inhibitors 1e, 2e, 3e, 4e and 5e exerted the anti-proliferative activities against CTCL cell lines at 20- 100 µM concentrations. Both the pyrimidine- and pyridine-based probes exhibited μM inhibitory activity against HDAC8. The pyrimidine-based probe 1e displayed remarkable HDAC8 selectivity superior to that of the standard drug, SAHA with an IC50 at 0.1µM.Conclusion:Our study demonstrated that simple modifications at different portions of pharmacophore in the hydroxamic acid analogues are effective for improving both HDAC8 inhibitory activity and isoform selectivity. Potent and highly isoform-selective HDAC8 inhibitors were identified. These findings would be expedient for further development of HDAC8-selective inhibitors.

The development of formulations with therapeutic peptides has been restricted to poor cell penetration and in this attempt; we developed pACC1 peptide loaded chitosan nanoparticles. The prepared nanoparticles were characterized with FT-IR, XRD, SEM and TEM. In addition, the suitable formulation was evaluated for hemocompatibility, plasma stability and embryo toxicity using Danio rerio embryo model. The results showed that pACC1 peptide loaded chitosan nanoparticles were compatible with plasma. They possess sustained release pattern and also found to be safe up to 300 mg/L in embryo toxicity tests. Cytotoxicity assays with MDA-MB-231 cell lines suggested that, pACC1 peptide loaded chitosan nanoparticles were capable of enhanced cellular penetration and reduced palmitic acid content, which was confirmed by H1 NMR. Hence, these nanoparticles could be employed as excellent adjuvant therapeutics while treating solid tumors with multi-drug resistance.

Two aromatic diimide-diol monomers N,N′-bis(4-hydroxynaphthyl)oxydiphthalic diimide and N,N′-bis(4-hydroxynaphthyl)biphenyl tetracarboxylic diimide were synthesized from aromatic dianhydrides and 5-amino1-naphthol. Polyimides (PIs) and co-polyimides (co-PIs) were synthesized from these new diols and 4,4′-dichlorodiphenyl sulfone through nucleophilic displacement reaction. The structures of the monomers and PIs and co-PIs were characterized by FT-IR and NMR analysis. The PIs and co-PIs were characterized by X-ray diffraction (XRD), thermogravimetry, differential scanning calorimetry, solution viscosity, solubility test, and dielectric properties test. XRD studies indicated that these PIs and co-PIs were amorphous in nature and were soluble in organic solvents. The PIs and co-PIs showed excellent thermal stability and the 10% weight loss occurred in the range 390–452 °C. The limiting oxygen index values of these PIs and co-PIs were in the range 37.9–42.3 and the value suggests that these PIs and co-PIs can ...

CuS nano/microstructures with different morphologies, such as solid microspheres with blocks (1-CuS), nanospheres (2-CuS) and microspheres of nanoflakes (3-CuS), were synthesized using alanine based coordinating ligands (1–3) as structure controlling agents in hydrothermal synthesis. Interestingly, copper coordination polymers (4 and 5) that were prepared using the same ligand (2) but differed subtly in the coordination and water molecule presence produced distinctly different nano/microstructures. Hydrogen-bonded network polymer 4 gave CuS microspheres composed of nanocrystals (4-CuS) whereas coordination network polymer without water molecules 5 yielded nanocrystalline powdered materials (5-CuS). Importantly, the synthesised CuS nano/microcrystals exhibited dye degradation (methylene blue (MB), methyl orange (MO) and Rhodamine blue (RB)) at room temperature without using any specific light source. The CuS nano/microcrystals also showed morphology dependent dye degradation properties. The most efficient dye degradation was observed for nanosphere 2-CuS whereas 1-CuS and 4-CuS exhibited comparatively slow dye degradation. Thus, the present work demonstrates the utility of simple coordinating ligands and subtle changes in the coordination network for tuning CuS morphologies which showed morphology dependent dye degradation.

The recently published CRAFT (complete reduction to amplitude frequency table) technique converts the raw FID data (i.e., time domain data) into a table of frequencies, amplitudes, decay rate constants, and phases. It offers an alternate approach to decimate time-domain data, with minimal preprocessing step. It has been shown that application of CRAFT technique to process the t1 dimension of the 2D data significantly improved the detectable resolution by its ability to analyze without the use of ubiquitous apodization of extensively zero-filled data. It was noted earlier that CRAFT did not resolve sinusoids that were not already resolvable in time-domain (i.e., t1 max dependent resolution). We present a combined NUS-IST-CRAFT approach wherein the NUS acquisition technique (sparse sampling technique) increases the intrinsic resolution in time-domain (by increasing t1 max), IST fills the gap in the sparse sampling, and CRAFT processing extracts the information without loss due to any severe apodization. NUS and CRAFT are thus complementary techniques to improve intrinsic and usable resolution. We show that significant improvement can be achieved with this combination over conventional NUS-IST processing. With reasonable sensitivity, the models can be extended to significantly higher t1 max to generate an indirect-DEPT spectrum that rivals the direct observe counterpart.

A new Schiff base ligand based on triphenylamine (1) was synthesized and demonstrated solvent dependent selective fluorescence sensing of Mg 2 + and Fe 3 + ions up to ppm level (10 − 6 M). Highly selective turn-on fluorescence for Mg 2 + was observed in DMSO as well as DMF (λ max = 506 nm, Φ = 0.007 (1), 0.17 (1 + Mg 2 + )). Interestingly, in THF, 1 showed strong turn-on fluorescence for Fe 3 + (blue, λ max = 460 nm, Φ = 0.064) as well as for Mg 2 + (greenish yellow). Interference studies confirm that Ca 2 + that strongly competes with Mg 2 + sensing had negligible interference. The practical application of 1 for selective fluorescence sensing of Mg 2 + from different water samples has also been demonstrated.

At present, the majority of established treatments for breast cancer are based on clinical manifestations, some fundamental of molecular and cellular biology of cancer. In recent times, the therapy is moving towards personalized medicines. Nevertheless, both the methodologies have own demerits. In the present study, we proposed a novel idea of targeted therapy with twin pharmacological potential by a peptide pACC1. The peptide was formulated with chitosan and evaluated with DMBA induced mammary carcinoma. Results suggest that the peptide holds great control on tumor cell multiplication, fatty acid synthesis and lactate levels. In addition, peptide also brings normal metabolic signs in glycolytic and glycogenic pathways. Histological studies confirm the dual pharmacological actions. Further, it is also proven that the peptide controls membrane receptor levels of HER2 and EGFR. In conclusion, that the peptide pACC1 could be employed as greater therapeutic adjuvant with currently established drugs without considering the stage of the cancer.

In this work, we report a completely green chemistry approach to synthesize silver nanoparticles (AgNPs) using the compound β-sitosterol-D-glucopyranoside (BS) isolated from the Indian sacred grass Desmostachya bipinnata, using natural sunlight as the initiator. BS synthesizes the AgNPs, in a free radical exchange process involving reactive oxygen species. The possible mechanism of the influence of BS on the reduction and stabilization of AgNPs is also discussed. The optical properties and morphology of the AgNPs were characterized by absorption spectroscopy and transmission electron microscopy. These bio-inspired AgNPs exhibited good catalytic activity during the catalytic degradation of environmentally hazardous organic dyes like methylene blue, methyl red, Congo red and acridine orange, in aqueous media.

We have herein computationally examined binding affinities and specificity of 2-hydroxy-3,5-dinitrobenzamide (HDNB), a small chemical molecular BH3-mimetic identified by means of ‘peptidodynmimetic method’, on the BH3-binding grooves of six anti-apoptotic proteins (Bcl-2, Bcl-B, Bcl-W, Bcl-XL, Bfl-1 and Mcl-1) from human beings. The HDNB ligand was found to interact on the BH3-binding grooves of Bcl-2, Bcl-B, Bcl-XL, Bfl-1 and Mcl-1, whereas it did not act as BH3-mimetic to Bcl-W. Moreover, binding affinities of the HDNB towards the anti-apoptotic proteins were significantly different from each other. The differential binding affinities and specificity of the HDNB towards the anti-apoptotic proteins have been chiefly attributed to the differences in the chemical properties of BH3-binding grooves of the proteins. Implications of the study to design efficient de novo antagonists to the anti-apoptotic proteins using the HDNB as seed molecule have been discussed. DOI: http://dx.doi.org/10.3329/bjp.v9i3.18965