Synthesis and antibacterial evaluation of nitrogen containing novel heterocyclic chalcones

<p>Thirteen different novel heterocyclic chalcones were synthesized using cycloaddition and Claisen–Schmidt condensation reactions. These newly synthesized compounds were characterized by their spectral studies and structure of (<i>E</i>)-3-(4-methoxyphenyl)-1-(5-methyl-1-(pyridin-3-yl)-1<i>H</i>-1,2,3-triazol-4-yl)prop-2-en-1-one (<b>4h</b>) was also evidenced by single crystal X-ray studies. These compounds were evaluated for antibacterial activities against seven bacterial strains <i>in vitro</i>. Compounds <b>4b</b> and <b>4c</b> containing 4-fluoro and 4-chloro groups have shown remarkable inhibition as showed by the standard drug ciprofloxacin against <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>, respectively. Another compound <b>4k</b> containing 3,4,5-trimethoxy group also showed similar activity against both these strains. Beside these three potential compounds <b>4b, 4c, 4k</b>, one more compound <b>4g</b> containing 4-methyl group showed equivalent inhibition as that of standard drug against <i>E. coli.</i> These categories of compounds are therefore good candidates for developing new effective antibacterial in future.</p

Enhanced Biopharmaceutical Performance of Rivaroxaban through Polymeric Amorphous Solid Dispersion

Rivaroxaban (RXB) is an orally active direct inhibitor of the activated serine protease Factor Xa, given as monotherapy in the treatment of venous thromboembolism (VTE). It has been characterized <i>in vitro</i> as a substrate for the active, nonsaturable efflux via P-gp transporter, limiting its high permeability. Therefore, the role of P-gp inhibiting polymers in enhancing the biopharmaceutical performance of RXB by preparing polymeric amorphous solid dispersion and subsequent improvement in solubility and permeability was investigated. Initially, solubility parameter and Flory–Huggins interaction parameter were determined for miscibility studies between drug and polymers. Binary dispersions were prepared by dissolving drug with polymers eudragit S100, eudragit L100, and soluplus in common solvent (5% v/v water in tetrahydrofuran) using spray dryer. Prepared binary dispersions were analyzed by differential scanning calorimetry (DSC), microscopy, powder X-ray diffractometry (PXRD), Fourier transform infrared spectroscopy (FTIR), dynamic vapor sorption (DVS), and solution nuclear magnetic resonance (NMR) spectroscopy. Superior performance of binary dispersions was observed upon dissolution and solubility studies over micronized active pharmaceutical ingredient. Amorphous solid dispersion (ASD) prepared with soluplus showed 10-fold increase in apparent solubility and maintenance of supersaturation for 24 h compared to the crystalline RXB. Further, pharmacokinetic study performed in animals was in good correlation with the solubility data. Increases of 5.7- and 6.7-fold were observed in AUC and C_max, respectively, for ASDs prepared with soluplus compared to those with crystalline RXB. FTIR and NMR spectroscopy unveiled the involvement of N–H group of RXB with CO group of polymers in intermolecular interactions. The decreased drug efflux ratio was observed for ASDs prepared with eudragit S100 and soluplus in Caco-2 transport study suggesting improvement in the absorption of RXB. Hence, the present study demonstrates ASD using soluplus as a promising formulation strategy for enhancing the biopharmaceutical performance of RXB by increasing the solubility and circumventing the P-gp activity

Synthesis and evaluation of antibacterial and antioxidant activity of novel 2-phenyl-quinoline analogs derivatized at position 4 with aromatically substituted 4<i>H</i>-1,2,4-triazoles

<p>A set of novel quinolone–triazole conjugates (<b>12</b>–<b>31</b>) were synthesized in three steps in good yields starting from 2-phenylquinoline-4-carboxylic acid. All the intermediates, as well as the final 1,2,4-triazolyl quinolines were fully characterized by their detailed spectral analysis utilizing different techniques such as IR, ¹H NMR, ¹³C NMR, and finally mass spectrometry. All the synthesized compounds were evaluated <i>in vitro</i> for their potential antibacterial activity and their preliminary safety profile was assessed through cytotoxicity assay. Additionally, six selected conjugates were evaluated for their antioxidative properties on the basis of density functional theory calculations, using radical scavenging assay (DPPH) and cellular antioxidant assay. The reported results encourage further investigation of selected compounds and are shading light on their potential pharmacological use.</p