Utility of oxidation-reduction reaction for the determination of ranitidine hydrochloride in pure form,in dosage forms and in the presence of its oxidative degradates

Three simple, accurate and sensitive colorimetric methods (A, B and C) for the determination of ranitidine HCl (RHCl) in bulk sample, in dosage forms and in the presence of its oxidative degradates are described. The first method A is based on the oxidation of the drug by N-bromosuccinimide (NBS) and determination of the unreacted NBS by measurement of the decrease in absorbance of amaranth dye (AM) at a suitable lambda(max)=520 nm. The methods B and C involve the addition of excess Ce(4+) and determination of the unreacted oxidant by decrease the red color of chromotrope 2R (C2R) at a suitable lambda(max)=528 nm for method B or decrease the orange pink color of rhodamine 6G (Rh6G) at a suitable lambda(max)=526 nm for method C. Regression analysis of Beer-Lambert plots showed good correlation in the concentration ranges 0.2-3.6, 0.1-2.8 and 0.1-2.6 microg ml(-1) for methods A, B and C, respectively. The apparent molar absorptivity. Sandell sensitivity, detection and quantitation limits were calculated. For more accurate results, Ringbom optimum concentration ranges were 0.3-3.4, 0.2-2.6 and 0.2-2.4 microg ml(-1) for methods A, B and C, respectively. Analyzing pure and dosage forms containing RHCl tested the validity of the proposed methods. The relative standard deviations were 相似文献   

Molecular dynamics simulation study of the negative correlation in antibody AZ28-catalyzed oxy-cope rearrangement

The oxy-Cope rearrangement reaction in the antibody AZ28 is investigated using ab initio molecular orbital calculations and molecular mechanical molecular dynamics simulations. This antibody, AZ28, is known as one of the few systems where the mature catalytic antibody shows a negative correlation between the transition state analogue (TSA) binding affinity and the catalytic rate of the oxy-Cope rearrangement compared to the germ line catalytic antibody. The ab initio optimized structure shows that the transition state structure has a more planar configuration than the TSA. The favorable electrostatic interactions between AZ28 and the transition state analogue overcome the unfavorable van der Waals interactions; thus, AZ28 shows higher binding affinity for the TSA than the germ line. However, the AZ28 is not flexible enough to accept the relatively planar transition state structure. Because the lower flexibility causes poorer antibody-hapten interaction energies, the activation free energy of the oxy-Cope rearrangement becomes larger in the mature antibody than the germ line. We show that the differences in flexibility between the germ line and the mature form and the differences in structure between TSA and the transition state are the origin of the negative correlation in AZ28-catalyzed oxy-Cope rearrangement. The mutation of residue 34 of the light chain, 34(L), affects the binding free energies through the interresidue interaction because it is the closest to the hapten among the six mutatable residues. However, it does not affect the negative correlation.     

Refinement of the NMR structures of alpha-conotoxin MI using molecular dynamics simulation with explicit solvent water and a full molecular force field

Three NMR structures of alpha-conotoxin MI, a potent antagonist of the nicotinic acetylcholine receptor, have been refined using molecular dynamics (MD) simulation with explicit water. Although the convergence of the NMR structures of alpha-conotoxin MI was not sufficient to provide detailed structural features, the average structures obtained from MD simulations converged to one conformation, providing structural characteristics. The resulting structure was also found to be consistent with the results of amide proton-exchange experiments. These results demonstrate that MD simulation with explicit solvent water is very useful in refining NMR structures.     

Spectrophotometric determination of hyoscine butylbromide and famciclovir in pure form and in pharmaceutical formulations

A simple, rapid, and extractive spectrophotometric method was developed for the determination of hyoscine butylbromide (HBB) and famciclovir (FCV) in pure and pharmaceutical formulations. These methods are based on the formation of yellow ion-pair complexes between the basic nitrogen of the drug and four sulphonphthalein acid dyes, namely; bromocresol green (BCG), bromothymol blue (BTB), bromocresol purple (BCP) and bromophenol blue (BPB) in phthalate buffer of pH range (3.0-3.5). The formed complexes were extracted with chloroform and measured at 420, 412, 409 and 415nm for HBB and at 418, 412, 407 and 414nm for FCV using BCG, BTB, BCP and BPB, respectively. The analytical parameters and their effects on the reported systems are investigated. Beer's law was obeyed in the range 1.0-20mugmL(-1) with correlation coefficient (n=6)>/=0.9997. The molar absorptivity, Sandell sensitivity, detection and quantification limits were also calculated. The composition of the ion pairs was found 1:1 by Job's method in all cases and the conditional stability constant (K(f)) of the complexes have been calculated. The free energy changes (DeltaG) were determined for all complexes formed. The proposed methods have been applied successfully for the analysis of the studied drugs in pure and pharmaceutical formulations with percentage recoveries ranges from 99.84 to 100.26. The results were in good agreement with those obtained by the official methods.     

Icotinib,Almonertinib, and Olmutinib: A 2D Similarity/Docking-Based Study to Predict the Potential Binding Modes and Interactions into EGFR

In the current study, a 2D similarity/docking-based study was used to predict the potential binding modes of icotinib, almonertinib, and olmutinib into EGFR. The similarity search of icotinib, almonertinib, and olmutinib against a database of 154 EGFR ligands revealed the highest similarity scores with erlotinib (0.9333), osimertinib (0.9487), and WZ4003 (0.8421), respectively. In addition, the results of the docking study of the three drugs into EGFR revealed high binding free energies (ΔG_b = −6.32 to −8.42 kcal/mol) compared to the co-crystallized ligands (ΔG_b = −7.03 to −8.07 kcal/mol). Analysis of the top-scoring poses of the three drugs was done to identify their potential binding modes. The distances between Cys797 in EGFR and the Michael acceptor sites in almonertinib and olmutinib were determined. In conclusion, the results could provide insights into the potential binding characteristics of the three drugs into EGFR which could help in the design of new more potent analogs.     

DNA Binding and Antitumor Activity of a New Fluorescent Probe Eu(Ⅲ)-Complex Containing 4-Methyl-Coumarin Moiety

A new europium (Ⅲ) complex containing (4-Methyl-2-oxo-2H-chromen-7-yloxy)-acetic acid moiety (CMMC) was synthesized, characterized, and confirmed as antitumor agent and fluorescent probe. The spectroscopic measurements of Eu(Ⅲ) in the presence of CMMC were obtained in different solvents. The results show that the strongest Eu(Ⅲ) emission bands were monitored in iso-propyl alcohol while the weakest Eu(Ⅲ) emission band was observed in acetonitrile. The interaction of Eu(Ⅲ)-(CMMC)₂ complex with DNA was monitored using absorption and emission techniques. From fluorescence titration measurements, the binding constants of DNA with Eu(Ⅲ)-(CMMC)₂ complex were found to be 1.04×105 L·mol-1 in Tris-HCl and 1.17×107 L·mol-1 in DMSO-Tris-HCl buffer (9∶1 V/V). Hypochromism was observed from the absorption titration experiment which indicates the intercalation of Eu(Ⅲ)-complex between the base pair of DNA. This result further confirmed by fluorescent Ethidium bromide displacement assay. The fluorescence calibration curve was used for the determination of DNA with LOD of 1.2 ng in DMSO-Tris-HCl buffer (9∶1 V/V) and 5 ng in Tris-HCl buffer. The preliminary antitumor investigation shows promising cytotoxicity against MDA-MB-231, MCF-7 (mammary cancer), and PC-3 (prostate carcinoma) cell lines with IC₅₀ values of 40.63, 25.42 and 30.25 μmol·L-1, respectively.     

An overview of the synthetic routes to Faipiravir and their analogous

The biological and medicinal properties of Favipiravir and its analogs have prompted enormous research aimed at developing synthetic routes to these heterocycles. This review focuses on the chemical properties associated with this system.     

Overview of the synthetic routes to sildenafil and its analogues

The biological and medicinal properties of sildenafil and its analogues have prompted enormous research aimed at developing synthetic routes to these heterocycles. This review focuses on the chemical properties associated with this system.     

Recent Advances in the Chemistry and Synthetic Uses of Amino‐1,3,4‐thiadiazoles

Amino‐1,3,4‐thiadiazoles, although scarce in nature, constitute a group of nitrogen and sulfur heterocyclic compounds that have shown significant biological activities. Their transformations into other biologically active compounds have been exploited. This review describes the work on the synthesis and reactions of amino‐1,3,4‐thiadiazoles as well as their biological evaluation.