Studies on synthetic and structural characterization of new fluorine substituted phthalides of pharmaceutical interest.

An efficient and economical synthesis of some new fluorine substituted phthalides was accomplished from two γ-keto acids, 2-(4-fluorobenzoyl)benzoic acid and 2-(3,5-dinitro-4-flurobenzoyl)benzoic acid. Each acid was reacted with various phenolic compounds in presence of catalytic quantity of concentrated sulphuric acid to get the phthalides. The structures of the synthesized compounds were established on the basis of their elemental analysis, spectral data and chemical reactions. Some of the synthesized phthalides exhibited antibacterial and antifungal activity on antimicrobial screening against human pathogenic bacteria and fungi.

Spectral investigation of the effect of anion on the stability of non covalent assemblies of 2,3,5,6,8,9,11,12-octahydro-1,4,7,10,13-benzopentaoxacyclopentadecine (benzo-15-crown-5) with sodium halides.

A series of complexes of 2,3,5,6,8,9,11,12-octahydro-1,4,7,10,13-benzopentaoxacyclopentadecine (benzo-15-crown-5) with sodium halides was synthesized in acetonitrile. The effect of anion on the stability and spectral properties of complexes of benzo-15-crown-5 with sodium halides was investigated. The synthesis of complexes of sodium fluoride and sodium chloride are reported for the first time. Chloroform was used as solvent to study the assembly in solution state by 1H and 13C NMR techniques. Single crystal diffraction studies on the easily crystallizable bromide complex confirmed 1:1 stoichiometry of the complex. IR and Raman studies provided valuable evidence for a water molecule shared between the crown encapsulated cation and the counter ion to give a solvent shared ion pair (SSIP). The fluorescence spectra of the complexes were obtained in chloroform by excitation at 270nm to study the effect of complexation on the fluorescent properties of benzo-15-crown-5.

Synthesis of 4-piperidone Based Curcuminoids with Anti-inflammatory and Anti-Proliferation Potential in Human Cancer Cell Lines.

A series of 4-piperidone based curcuminoids were synthesized and anticancer potential of these compounds was evaluated against human myeloid leukemia (KBM5) and colon cancer (HCT116) cell lines. Their anti-inflammatory potential was determined through the down-regulation of tumor necrosis factor (TNF)-α-induced nuclear factor (NF)-κB. All compounds, except one, were found to exhibit better cytotoxicity than curcumin at 5 µM. Furthermore, many compounds have shown good potential to inhibit the TNF-α-induced NF-κB activation. Docking study of the compounds with NF-κB revealed that the binding affinity of the compounds ranged from ‒9.0 to ‒6.5 kcal/mol with 0-8 H-bonds. It was also observed that amido-ether based mono-carbonyl compounds bound around the same region of NF-κB where polynucleotides are known to bind to exhibit their activity.

Novel metronidazole-chalcone conjugates with potential to counter drug resistance in Trichomonas vaginalis.

Trichomoniasis is the most prevalent, curable sexually transmitted disease (STD), which increases risk of viral STDs and HIV. However, drug resistance has been developed by some strains of Trichomonas vaginalis against Metronidazole (MTZ), the FDA approved drug against trichomoniasis. In the present study twenty two chalcone hybrids of metronidazole have been synthesized in a quest to get new molecules with higher potential against metronidazole-resistant T. vaginalis. All new hybrid molecules were found active against T. vaginalis with varying levels of activity against MTZ-susceptible and resistant strains. Eight compounds (4a, 4c, 4d, 4e, 4f, 4h, 4q and 4s) were found as active as the standard drug with an MIC of 1.56 µg/ml against MTZ-susceptible strain. However, compounds 4e, 4h and 4m were 4-times more active than MTZ against drug-resistant T. vaginalis, amongst which 4e and 4h were most promising against both susceptible and resistant strains.

Synthesis, characterization and in vitro anticancer activity of C-5 curcumin analogues with potential to inhibit TNF-α-induced NF-κB activation.

In a search of new compounds active against cancer, synthesis of a series of C-5 curcumin analogues was carried out. The new compounds demonstrated good cytotoxicity against chronic myeloid leukemia (KBM5) and colon cancer (HCT116) cell lines. Further, these compounds were found to have better potential to inhibit TNF-α-induced NF-κB activation in comparison to curcumin, which show their potential to act as anti-inflammatory agents. Some compounds were found to show higher cytotoxicity against cancer cell lines in comparison to curcumin used as standard.

Solvatochromic and single crystal studies of 3-(4-bromophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde.

The structure of 3-(4-bromophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde was determined by using X-ray diffraction analysis. Photophysical studies of the title compound were investigated in the solvents with different polarities. The emission spectrum of the compound was recorded in polar solvent DMSO (356 nm). In different solvents the extinction coefficients and quantum yield of the compound vary from 1.88×10(4) to 3.53×10(4) and 0.01 to 0.25, respectively. The ratio of the dipole moment of excited state to the dipole moment of ground state was calculated by using solvatochromic shift methods.

Rutin-phospholipid complex: an innovative technique in novel drug delivery system- NDDS.

Biopharmaceutical properties together with potency contribute critically towards clinical efficacy of the drugs by influencing the dissolution and bioavailability. The aim of this study was to develop an amphiphilic phyto-phospholipid complex in order to enhance the delivery of poorly soluble rutin. The rutin-phospholipid complex (Ru-PLc) was prepared and investigated for various physico-chemical parameters like drug loading, infrared absorption (FTIR), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), scanning electron microscopy (SEM), aqueous/ n-octanol solubility and dissolution study. The in vitro anti-oxidant activity was also studied. In the SEM, Ru-PLc was found fluffy and porous with rough surface morphology. FTIR, DSC and XRPD data confirmed the formation of phospholipid complex. The water/ noctanol solubility of rutin was improved from 2.88 to 45.71 µg/ ml and 68.17 to 245.18 µg/ ml, respectively in the complex. The improved dissolution was shown by the phospholipid complex at different pH buffers. The antioxidant activity indicated that, the bioactivity of rutin was maintained even after being complexed with the phospholipid. Based on the results, it can be concluded that the phospholipid complex may be considered as a promising drug delivery system for improving the overall absorption and bioavailability of the rutin molecule.

Quantization of Dextromethorphan and Levocetirizine in Combined Dosage form Using a Novel Validated RP-HPLC Method.

The present study reveals a simple isocratic RP-HPLC method for the simultaneous determination of dextromethorphan hydrobromide and levocetirizine dihydrochloride in a cough syrup. The separation of these compounds was achieved within 10 min on a Phenomenex (USA) C(18) analytical column, 250×4.0 mm i.d., using an isocratic mobile phase consisting of potassium dihydrogen phosphate buffer (pH 2.5) - acetonitrile- tetrahydrofuran (70:25:5, v/v/v). The analysis was performed at a flow rate of 1.2 ml/min and at a detection wavelength of 232 nm. Percentage recovery and RSD were 100.36% and 0.05% for levocetirizine dihydrochloride, 100.35% and 0.27% for dextromethorphan hydrobromide respectively. Quantification of the components in syrup formulation was calculated against the peak areas of freshly prepared standard solutions. The method was validated as per ICH guidelines.

Determination of trace elements in Rheum moorcroftianum by AAS.

Micro and macro elements such as Zn, Cu, Mn, Fe, Co, Na, K, Ca and Li were detected from Rheum moorcroftianum Royle, a plant used in folk medicines. Altitudinal and seasonal variation of these trace elements in cultivated and wild roots and leaves of R. moorcroftianum were quantified by atomic absorption spectroscopy. The highest concentrations of Zn, Cu, Mn, Fe, Co, Na, K, Ca and Li were found to be 376.0 ± 0.9, 83.0 ± 4.6, 322.0 ± 6.0, 920.0 ± 1.9, 72.0 ± 1.5, 402.0 ± 7.8, 10,235.0 ± 7.0, 12,336.0 ± 2.6 and 59.9 ± 0.3 mg kg(-1), respectively, in all the samples analysed.

High-performance liquid chromatography analysis of plant saponins: An update 2005-2010.

Saponins are widely distributed in plant kingdom. In view of their wide range of biological activities and occurrence as complex mixtures, saponins have been purified and separated by high-performance liquid chromatography using reverse-phase columns at lower wavelength. Mostly, saponins are not detected by ultraviolet detector due to lack of chromophores. Electrospray ionization mass spectrometry, diode array detector , evaporative light scattering detection, and charged aerosols have been used for overcoming the detection problem of saponins.

Synthesis, characterization and fluorescence studies of 3,5-diaryl substituted 2-pyrazolines.

A series of 2-pyrazolines have been synthesized from α, ß unsaturated ketones and hydrazine hydrate with acetic/formic acid in ethanol/DMSO. The structures of 2-pyrazolines have been established by spectroscopic techniques i.e. UV, IR, (1)H NMR, (13)C NMR and micro element analysis. Fluorescence spectra were recorded in the solution at fixed concentration and same excitation wavelength at 290 nm. The absorption band positions of all the compounds broadly lie between 280 and 336 nm and fluorescence band positions in the range between 300 and 370 nm, the near ultraviolet region.

Study on the trace elements in Swertia chirayita (Roxb.) H. Karsten.

An attempt has been made to analyze some trace elements and electrolytes like Zn, Cu, Mn, Fe, Co, Na, K, Ca, and Li present in the Swertia chirayita roots and leaves. The concentration of Ca in all the samples was more than 1,346.0 mg/kg and the concentration of other elements was found in the order K > Ca > Fe > Na > Mn > Zn > Co > Cu > Li in different samples of S. chirayita.

Semecarpus anacardium Linn.: A review.

Semecarpus anacardium Linn. (Family: Anacardiaceae), commonly known 'Ballataka' or 'Bhilwa', has been used in various traditional system of medicines for various ailments since ancient times. Its nuts contain a variety of biologically active compounds such as biflavonoids, phenolic compounds, bhilawanols, minerals, vitamins and amino acids, which show various medicinal properties. The fruit and nut extract shows various activities like antiatherogenic, antiinflammatory, antioxidant, antimicrobial, anti-reproductive, CNS stimulant, hypoglycemic, anticarcinogenic and hair growth promoter. The article reviews the various activities of the plant.

Development and evaluation of pharmacosomes of aceclofenac.

Pharmacosomes are amphiphilic lipid vesicular systems containing phospholipid complexes with a potential to improve bioavailability of poorly water soluble as well as poorly lipophilic drugs. To improve the water solubility, bioavailability and minimize the gastrointestinal toxicity of aceclofenac, its pharmacosomes were prepared. Aceclofenac was complexed with phosphatidylcholine (80%) in two different ratios (1:1 and 2:1) using conventional solvent evaporation technique. Pharmacosomes thus prepared were subjected to solubility and drug content evaluation, scanning electron microscopy, differential scanning calorimetry, X ray powder diffraction and in vitro dissolution study. Pharmacosomes of aceclofenac were found to be disc shaped with rough surface in scanning electron microscopy. Drug content was found to be 91.88% (w/w) for aceclofenac phospholipid complex (1:1) and 89.03% (w/w) aceclofenac-phospholipid complex (2:1). Differential scanning calorimetric thermograms and X ray powder diffraction datas confirmed the formation of phospholipid complex. Solubility and dissolution profile of the prepared complex was found to be much better than aceclofenac.

Synthesis, Structure Activity Relationship Studies and Pharmacological Evaluation of 2-Phenyl-3-(Substituted Phenyl)-3H-Quinazolin-4-ones as Serotonin 5-HT(2) Antagonists.

Benzoyl chloride was added to the solution of anthranilic acid in pyridine to afford crude 2-phenyl-benzo[d][1, 3] oxazin-4-one (1). To the solution of compound 1 in dry toluene, various substituted anilines were added and the mixture refluxed for 8 h to afford 2-phenyl-3-(substituted phenyl)-3H-quinazolin-4-ones (2a-2f). All the compounds were obtained in solid state in yields varying between 40 to 70%. Spectral characterization included FTIR, (1)H NMR and Electrospray MS. The synthesized compounds were screened for 5-HT(2) antagonist activity. Some of the title compounds have been found to show significant 5-HT(2) antagonist activity. The compound 2b, 3-(2-chlorophenyl)-2-phenyl-3H-quinazolin-4-one was the most potent derivative in the series of compound synthesized.

Development and physicochemical evaluation of pharmacosomes of diclofenac.

Pharmacosomes are amphiphilic lipid vesicular systems that have shown their potential in improving the bioavailability of poorly water soluble as well as poorly lipophilic drugs. Diclofenac is a poorly water soluble drug and also causes gastrointestinal toxicity. To improve the water solublity of diclofenac, its pharmacosomes (phospholipid complex) have been prepared and evaluated for physicochemical analysis. Diclofenac was complexed with phosphatidylcholine (80%) in equimolar ratio, in the presence of dichloromethane, by the conventional solvent evaporation technique. Pharmacosomes thus prepared were evaluated for drug solubility, drug content, surface morphology (by scanning electron microscopy), phase transition behaviour (by differential scanning calorimetry), crystallinity (by X-ray powder diffraction) and in vitro dissolution. Pharmacosomes of diclofenac were found to be irregular or disc shaped with rough surfaces in SEM. Drug content was found to be 96.2 +/- 1.1%. DSC thermograms and XRPD data confirmed the formation of the phospholipid complex. Water solubility of the prepared complex was found to be 22.1 microg mL-1 as compared to 10.5 microg mL-1 of diclofenac. This improvement in water solubility in prepared pharmacosomes may result in improved dissolution and lower gastrointestinal toxicity. Pharmacosomes showed 87.8% while the free diclofenac acid showed a total of only 60.4% drug release at the end of 10 h of dissolution study.

Pharmacosomes: the lipid-based new drug delivery system.

Lipid-based drug delivery systems have been investigated in various studies and shown their potential in controlled and targeted drug delivery. Pharmacosomes are amphiphilic phospholipid complexes of drugs bearing active hydrogen that bind to phospholipids. Pharmacosomes impart better biopharmaceutical properties to the drug, resulting in improved bioavailability. Pharmacosomes have been prepared for various non-steroidal anti-inflammatory drugs, proteins, cardiovascular and antineoplastic drugs. Developing the pharmacosomes of the drugs has been found to improve the absorption and minimize the gastrointestinal toxicity. This article reviews the potential of pharmacosomes as a controlled and targeted drug delivery system and highlights the methods of preparation and characterization.