Pyridine clubbed coumarin analogues: Their synthesis and biological studies as antimicrobials and antioxidants

The major aim of this study is to develop the new class of coumarin candidate clubbed with dihydropyridine-3-carbonitrile with an improved potency as an antimicrobial and antioxidant agent. The key intermediate 6-nitro-4-methyl coumarin-yl chloro acetate 5 have been linked to the 6-(4-fluorophenyl)-2-oxo-4-phenyl-1,2-dihydro pyridine-3-carbonitrile IIa-j derivative to afford 4-methyl-6-nitro-2-oxo-2H-chromen-7-yl-2-(3-cyano-6-(4-fluoro phenyl)-4-(substituted-phenyl) pyridin-2-yl-oxy) acetates 7a-j via efficient organic transformations. All the new derivatives have been characterized by spectral studies (IR, 1H and 13C NMR and mass spectroscopy). In vitro antimicrobial activity have been carried out using the broth microdilution method and antioxidant potency using DPPH bioassays. Bioassay results reveal that compound 7e are equipotent against E. coli with MIC value 50 µg/ mL compared to standard drug ciprofoloxacin. A final analogue 7c with 4-chlorophenyl substituent indicated better antifungal potency against C. albicans with MIC value 100 µg/ mL compared to standard drug griseofulvin. In addition, newly synthesized analogues have been found to be significant scavengers of DPPH radical with IC50 values of 32.11 μg/mL. It has been observed that the potent antibacterial candidate has proved to possess significant antioxidant activity. The presence of chlorine and hydroxy group on phenyl ring plays an important role for the potency in above mentioned biological assay

Pyridine clubbed coumarin analogues: Their synthesis and biological studies as antimicrobials and antioxidants

1713-1720The major aim of this study is to develop the new class of coumarin candidate clubbed with dihydropyridine-3-carbonitrile with an improved potency as an antimicrobial and antioxidant agent. The key intermediate 6-nitro-4-methyl coumarin-yl chloro acetate 5 have been linked to the 6-(4-fluorophenyl)-2-oxo-4-phenyl-1,2-dihydro pyridine-3-carbonitrile IIa-j derivative to afford 4-methyl-6-nitro-2-oxo-2H-chromen-7-yl-2-(3-cyano-6-(4-fluoro phenyl)-4-(substituted-phenyl) pyridin-2-yl-oxy) acetates 7a-j via efficient organic transformations. All the new derivatives have been characterized by spectral studies (IR, 1H and 13C NMR and mass spectroscopy). In vitro antimicrobial activity have been carried out using the broth microdilution method and antioxidant potency using DPPH bioassays. Bioassay results reveal that compound 7e are equipotent against E. coli with MIC value 50 µg/ mL compared to standard drug ciprofoloxacin. A final analogue 7c with 4-chlorophenyl substituent indicated better antifungal potency against C. albicans with MIC value 100 µg/ mL compared to standard drug griseofulvin. In addition, newly synthesized analogues have been found to be significant scavengers of DPPH radical with IC50 values of 32.11 μg/mL. It has been observed that the potent antibacterial candidate has proved to possess significant antioxidant activity. The presence of chlorine and hydroxy group on phenyl ring plays an important role for the potency in above mentioned biological assay

Inhibitory Neurotransmission Is Sex-Dependently Affected by Tat Expression in Transgenic Mice and Suppressed by the Fatty Acid Amide Hydrolase Enzyme Inhibitor PF3845 via Cannabinoid Type-1 Receptor Mechanisms

(1) Background. The endocannabinoid (eCB) system, which regulates physiological and cognitive processes, presents a promising therapeutic target for treating HIV-associated neurocognitive disorders (HAND). Here we examine whether upregulating eCB tone has potential protective effects against HIV-1 Tat (a key HIV transactivator of transcription) protein-induced alterations in synaptic activity. (2) Methods. Whole-cell patch-clamp recordings were performed to assess inhibitory GABAergic neurotransmission in prefrontal cortex slices of Tat transgenic male and female mice, in the presence and absence of the fatty acid amide hydrolase (FAAH) enzyme inhibitor PF3845. Western blot and mass spectrometry analyses assessed alterations of cannabinoid receptor and enzyme protein expression as well as endogenous ligands, respectively, to determine the impact of Tat exposure on the eCB system. (3) Results. GABAergic activity was significantly altered upon Tat exposure based on sex, whereas the effectiveness of PF3845 to suppress GABAergic activity in Tat transgenic mice was not altered by Tat or sex and involved CB1R-related mechanisms that depended on calcium signaling. Additionally, our data indicated sex-dependent changes for AEA and related non-eCB lipids based on Tat induction. (4) Conclusion. Results highlight sex- and/or Tat-dependent alterations of GABAergic activity and eCB signaling in the prefrontal cortex of Tat transgenic mice and further increase our understanding about the role of FAAH inhibition in neuroHIV

Characterization of Keratin Microparticles from Feather Biomass with Potent Antioxidant and Anticancer Activities

In the present study chicken feathers were hydrolyzed by chemical treatment in alkaline conditions. The pH value of feather hydrolyzed solution was amended accordingly the iso-electric precipitation. Two types of keratin microparticles KM1, KM2 were synthesized under acidic conditions at 3.5 and 5.5 pH respectively. The synthesized keratin microparticles possessed uniform and round surface by scanning electron microscopy (SEM). The thermal degradation of microparticles were examined by thermogravimetry (TGA). Fourier transform infrared spectroscopy (FTIR) revealed that the extracted keratin retained the most of protein backbone. The microparticles were screened for their in vitro anticancer activities by SRB bioassay towards HeLa, SK-OV-3 and A549 cancer cell lines. Futhermore, their cytotoxicity towards healthy cell lines was analyzed having Malin Darby canine kidney (MDCK) cell lines along with in vitro antioxidant activity using DPPH and ABTS methods KM1 and KM2 showed 200.31 ± 1.01 and 139.73 ± 0.94, 214.16 ± 0.29 and 153.92 ± 0.61, 328.92 ± 3.46 and 200.33 ± 2.48 μg/mL of IC50 levels against HeLa, SK-OV-3, and A549 cell lines, respectively. Moreover, KM1 and KM2 demonstrated significant antioxidant potency with IC50 levels 13.15 and 9.02 μg/mL as well as 8.96 and 5.60 μg/mL in DPPH and ABTS radical scavenging bioassay, respectively

Molecular Docking Studies and Biological Evaluation of Berberine–Benzothiazole Derivatives as an Anti-Influenza Agent via Blocking of Neuraminidase

In this study, we have introduced newly synthesized substituted benzothiazole based berberine derivatives that have been analyzed for their in vitro and in silico biological properties. The activity towards various kinds of influenza virus strains by employing the cytopathic effect (CPE) and sulforhodamine B (SRB) assay. Several berberine–benzothiazole derivatives (BBDs), such as BBD1, BBD3, BBD4, BBD5, BBD7, and BBD11, demonstrated interesting anti-influenza virus activity on influenza A viruses (A/PR/8/34, A/Vic/3/75) and influenza B viral (B/Lee/40, and B/Maryland/1/59) strain, respectively. Furthermore, by testing neuraminidase activity (NA) with the neuraminidase assay kit, it was identified that BBD7 has potent neuraminidase activity. The molecular docking analysis further suggests that the BBD1–BBD14 compounds’ antiviral activity may be because of interaction with residues of NA, and the same as in oseltamivir

Molecular Docking Studies and Biological Evaluation of Berberine–Benzothiazole Derivatives as an Anti-Influenza Agent via Blocking of Neuraminidase

In this study, we have introduced newly synthesized substituted benzothiazole based berberine derivatives that have been analyzed for their in vitro and in silico biological properties. The activity towards various kinds of influenza virus strains by employing the cytopathic effect (CPE) and sulforhodamine B (SRB) assay. Several berberine–benzothiazole derivatives (BBDs), such as BBD1, BBD3, BBD4, BBD5, BBD7, and BBD11, demonstrated interesting anti-influenza virus activity on influenza A viruses (A/PR/8/34, A/Vic/3/75) and influenza B viral (B/Lee/40, and B/Maryland/1/59) strain, respectively. Furthermore, by testing neuraminidase activity (NA) with the neuraminidase assay kit, it was identified that BBD7 has potent neuraminidase activity. The molecular docking analysis further suggests that the BBD1–BBD14 compounds’ antiviral activity may be because of interaction with residues of NA, and the same as in oseltamivir

Green-Synthesis of Anisotropic Peptone-Silver Nanoparticles and Its Potential Application as Anti-Bacterial Agent

This study demonstrates a green-route-based synthesis of high-concentration suspensions of anisotropic silver nanoparticles (AgNPs) by peptone (Pep), a soluble protein hydrolysate and an abundantly used nutrient source in microbial-media. The transformation of Ag ions from solution into a high-concentration suspension of anisotropic Pep-AgNPs, at an extremely low concentration of peptone (0.02%), indicates that the present green-route synthesis method follows “low volume high concentration nano-synthesis„, and, hence, enhances the economic significance of the process. Process optimization with different concentrations of AgNPs (1⁻5 mM), NaOH solution (5⁻40 mM), and peptone (0.004%⁻0.12%) gave the optimized Pep-AgNPs synthesis at 3 mM of AgNO3, 20 mM of NaOH, and 0.02% of the peptone concentrations. The green-route synthesized Pep-AgNPs were structurally characterized by the TEM, XPS, FT-IR, and XRD analyses. The Pep-AgNPs against the clinically relevant bacteria Escherichia coli and Staphylococcus aureus gave significant anti-bacterial properties, with a MIC (minimum inhibitory concentration) of 100 ppm. The colony counting and morphological observation of the bacterial cell under SEM corroborated an anti-bacterial potential of the Pep-AgNPs. Therefore, Pep-AgNPs are green-route synthesized, anisotropic, and have a significant anti-bacterial potential that can be used in many relevant applications

Inhibitory Neurotransmission Is Sex-Dependently Affected by Tat Expression in Transgenic Mice and Suppressed by the Fatty Acid Amide Hydrolase Enzyme Inhibitor PF3845 via Cannabinoid Type-1 Receptor Mechanisms

(1) Background. The endocannabinoid (eCB) system, which regulates physiological and cognitive processes, presents a promising therapeutic target for treating HIV-associated neurocognitive disorders (HAND). Here we examine whether upregulating eCB tone has potential protective effects against HIV-1 Tat (a key HIV transactivator of transcription) protein-induced alterations in synaptic activity. (2) Methods. Whole-cell patch-clamp recordings were performed to assess inhibitory GABAergic neurotransmission in prefrontal cortex slices of Tat transgenic male and female mice, in the presence and absence of the fatty acid amide hydrolase (FAAH) enzyme inhibitor PF3845. Western blot and mass spectrometry analyses assessed alterations of cannabinoid receptor and enzyme protein expression as well as endogenous ligands, respectively, to determine the impact of Tat exposure on the eCB system. (3) Results. GABAergic activity was significantly altered upon Tat exposure based on sex, whereas the effectiveness of PF3845 to suppress GABAergic activity in Tat transgenic mice was not altered by Tat or sex and involved CB₁R-related mechanisms that depended on calcium signaling. Additionally, our data indicated sex-dependent changes for AEA and related non-eCB lipids based on Tat induction. (4) Conclusion. Results highlight sex- and/or Tat-dependent alterations of GABAergic activity and eCB signaling in the prefrontal cortex of Tat transgenic mice and further increase our understanding about the role of FAAH inhibition in neuroHIV