Comparative Liquid Chromatographic Study for Concurrent Determination of Canagliflozin and Metformin in Combined Tablets

New HPLC-UV method (method A), for simultaneous determination of metformin (MET) and canagliflozin (CANA), was developed and compared to another novel UPLC-UV method (method B) in their tablet combination. Concerning method A, isocratic separation was done by C18 column (100 mm × 2.1 mm, 3 μm) using methanol and 0.03 M phosphate buffer (75:25, v/v) at pH 3.2 as a mobile phase. Meanwhile, chromatographic separation in method B was achieved via Hypersil® gold (50 mm × 2.1 mm, 1.9 μm). Mobile phase was methanol and 0.03 M phosphate buffer at ratio of 80:20  v/v. In both, detection was done at wavelength of 240 nm. Method A showed satisfactory linearity results over 1–50 μg·mL−1 and 0.5–100 μg·mL−1, while method B linearity was at 0.1–50 μg·mL−1 and 0.25–100 μg·mL−1 for CANA and MET, respectively. In terms of accuracy and precision, method A accuracy was 99.81±0.73 and 99.37±0.54, while method B gave accuracy of 99.47±1.03 and 99.73±0.89 for CANA and MET, respectively. For precision, the % RSD was found to be less than 2% for three concentrations analyzed three times. The two methods are convenient for quality laboratories, yet the UPLC method offered the advantage of shorter run times and higher sensitivity

3-Ethoxymethyl-1,4-dihydroquinolin-4-one

In the title molecule, C12H13NO2, the dihydroquinolinone fused-ring system is nearly planar [maximum deviation = 0.012 (3) Å], and the mean plane passing through the extended ethoxymethyl substituent is aligned at 86.9 (2)° with respect to the fused-ring system. In the crystal, adjacent molecules are linked by an N—H...Ocarbonyl hydrogen bond to generate a chain running along the b-axis direction

Different Spectrophotometric Methods for Simultaneous Determination of Trelagliptin and Its Acid Degradation Product

New spectrophotometric and chemometric methods were carried out for the simultaneous assay of trelagliptin (TRG) and its acid degradation product (TAD) and applied successfully as a stability indicating assay to recently approved Zafatek® tablets. TAD was monitored using TLC to ensure complete degradation. Furthermore, HPLC was used to confirm dealing with one major acid degradation product. The proposed methods were developed by manipulating zero-order, first-derivative, and ratio spectra of TRG and TAD using simultaneous equation, first-derivative, and mean-centering methods, respectively. Using Spectra Manager II and Minitab v.14 software, the absorbance at 274 nm–260.4 nm, amplitudes at 260.4 nm–274.0 nm, and mean-centered values at 287.6 nm–257.2 nm were measured against methanol as a blank for TRG and TAD, respectively. Linearity and the other validation parameters were acceptable at concentration ranges of 5–50 μg/mL and 2.5–25 μg/mL for TRG and TAD, respectively. Using one-way analysis of variance (ANOVA), the optimized methods were compared and proved to be accurate for the simultaneous assay of TRG and TAD

QSAR-based rational discovery of novel substituted-4′-iminospiro[indoline-3,3′-[1,2,5]thiadiazolidinyl]-2-one 1′,1′-dioxide with potent in vitro anticancer activity

Abstract Recent studies have suggested that aldose reductase inhibition preferentially inhibits the growth of cancer cells. However, the investigations of this issue are not many. Novel nine substituted- 4′-iminospiro[indoline-3,3′-[1,2,5] thiadiazolidinyl]-2-one 1′,1′-dioxide derivatives were designed by both isosteric replacement of the imidazolidine-2,5-dione moiety in spirohydantoin scaffold and conformational rigidification approaches. A QSAR with high predictive power (r2 = 0.99) was created from a series of potent aldose reductase inhibitors and was used to predict the activity of our new compounds. Compound 5 showed the best docking score (− 33.24 kcal/mol) with the least RMSD value (< 1.5) obtained by molecular dynamic simulations over 20 ns. All compounds showed promising anticancer activities especially compound 5 that achieved the highest inhibitory activities with IC50; 0.013, 0.031, 0.064, and 0.048 mmol/L against breast, colon, prostate, and lung cell lines respectively. The discovery of this lead compound confirmed the rational design. Further investigations may be required for optimization of this compound

Synthesis and Cytotoxic Effect of Some Novel 1,2-Dihydropyridin-3-carbonitrile and Nicotinonitrile Derivatives

1-(2,4-Dichlorophenyl)-3-(4-fluorophenyl)propen-1-one (1) was prepared and reacted with an active methylene compound (ethyl cyanoacetate) in the presence of ammonium acetate to give the corresponding cyanopyridone 2. Compound 2 reacted with hydrazine hydrate, malononitrile, ethyl bromoacetate and phosphorous oxychloride to afford compounds 4 and 7–11, respectively. The 2-chloropyridine derivative 11 reacted with different primary amines, namely benzyl amine, piperonyl amine, 1-phenylethyl amine, and/or the secondary amines 2-methyl-pipridine and morpholine to give the corresponding derivatives 12–15. Hydrazinolysis of chloropyridine derivative 11 with hydrazine hydrate afforded the corresponding hydrazino derivative 17. Condensation of compound 17 with ethyl acetoacetate, acetylacetone, isatin and different aldehydes gave the corresponding derivatives 18–21. Some of newly synthesized compounds were screened for cytotoxic activity against three tumor cell lines. The results indicated that compounds 8 and 16 showed the best results, exhibiting the highest inhibitory effects towards the three tumor cell lines, which were higher than that of the reference doxorubicin and these compounds were non-cytotoxic towards normal cells (IC50 values &gt; 100 μg/mL)

Novel 6-Aminoquinazolinone Derivatives as Potential Cross GT1-4 HCV NS5B Inhibitors

Chronic hepatitis C virus (HCV) infections are a worldwide medical problem responsible for diverse types of liver diseases. The NS5B polymerase enzyme has become a very interesting target for the development of anti-HCV drugs owing to its fundamental role in viral replication. Here we report the synthesis of a novel series of 1-substituted phenyl-4(1H)-quinazolinone and 2-methyl-1-substituted phenyl-4(1H)-quinazolinone derivatives and evaluate their activity against HCV in HCV subgenomic replicon assays. The biological data revealed that compound 11a showed the highest activity against HCV GT1b at a micromolar concentration (EC50 = 0.984 &micro;M) followed by compound 11b (EC50 = 1.38 &micro;M). Both compounds 11a and 11b had high selectivity indices (SI = CC50/EC50), 160.71 and 71.75, respectively, which make them very interesting candidates for further development of more potent and selective anti-HCV agents

Synthesis, Molecular Docking and Preliminary in-Vitro Cytotoxic Evaluation of Some Substituted Tetrahydro-naphthalene (2&#039;,3&#039;,4&#039;,6&#039;-Tetra-O-Acetyl-β-D-Gluco/-Galactopyranosyl) Derivatives

A facile, convenient and high yielding synthesis of novel &lt;em&gt;S&lt;/em&gt;-glycosides and &lt;em&gt;N&lt;/em&gt;-glycosides incorporating 1,2,3,4-tetrahydronaphthalene and or 1,2-dihydropyridines moieties has been described. The aglycons &lt;strong&gt;2&lt;/strong&gt;, &lt;strong&gt;4&lt;/strong&gt;, and &lt;strong&gt;7&lt;/strong&gt; were coupled with different activated halosugars in the presence of basic and acidic medium. The preliminary &lt;em&gt;in-vitro&lt;/em&gt; cytotoxic evaluation&lt;strong&gt; &lt;/strong&gt;revealed that compounds &lt;strong&gt;3c&lt;/strong&gt;, &lt;strong&gt;3f&lt;/strong&gt;, &lt;strong&gt;5c&lt;/strong&gt; and &lt;strong&gt;7b&lt;/strong&gt; show promising activity. A molecular docking study was performed against tyrosine kinase (TK) (PDB code: 1t46) by Autodock Vina. The docking output was analyzed and some compounds have shown hydrogen bond (H-B) formation with reasonable distances ranged from 2.06 A° to 3.06 A° with Thr 670 and Cys 673 residues found in the specified pocket. No hydrogen bond was observed with either Glu 640 nor Asp 810 residues, as was expected from pdbsum