QSAR Studies of 6-Amino Uracil Base Analogues: A Thymidine Phosphorylase Inhibitor in Cancer Therapy

A novel series of 6-amino uracil base analogue were synthesized. QSAR study was used to relate the selective nonsubstrate inhibitory activity of 6-amino uracil base analogue with various physicochemical descriptors. Stepwise multiple regression analysis was performed to find out the correlation between various physicochemical descriptors and biological activity of the compounds by using Openstat 2 version 6.5.1 and valstat statistical software. Out of the several equations developed, the best equation having the highest significance was selected for further study. The equation is able to explain 60% of total variance and are more than 95% significant as revealed by the F value

Study of forced degradation behaviour of eprosartan mesylate and development of validated stability indicating assay method by UPLC

The present research work describes comprehensive stress testing of eprosartan mesylate (EM) according to ICH guideline Q1A (R2), and development of a stability-indicating reversed phase ultra performance liquid chromatographic (UPLC) assay. The drug was subjected to acid (0.5N HCl), neutral and alkaline (0.5 N NaOH) hydrolytic conditions at 80 °C, and to oxidative decomposition at room temperature. Photolysis was carried out by exposing the drug during the day time to sunlight (60,000-70,000 lux) for two days and oxidative study was performed with 0.5 mg/ml in 30 % hydrogen peroxide (H2O2 ) at room temperature for 25 hr. The solid drug was also subjected to 50 °C for 30 days in a hot air oven. Degradation of the drug was found to occur under alkaline, acidic and neutral hydrolytic conditions. Separation of the drug and the degradation products was successfully achieved on a BEH (bridged ethylene hybrid) C18 column (1.7 µm, 2.1 mm × 150 mm) with gradient elution of water-acetonitrile as mobile phase. The flow rate and detection wavelength were 0.1 ml/min and 232 nm, respectively. The method was validated and the response was found to be linear in the drug concentration range 5-25 µg/ml (r2 = 0.999). The %RSD in intra-day and inter-day precision studies was < 0.8 %. Recovery of the drug from a mixture of degradation products was between 98.3 and 99.8 %. The LOD and LOQ of developed method were obtained at 0.15 µg/ml and 0.45 µg/ml respectively. The method was specific to the drug, selective to degradation products, and robust. PDA purity test also confirmed the specificity of the method.Colegio de Farmacéuticos de la Provincia de Buenos Aire

RP-HPLC method for estimation and stability study of drotaverine HCl as per ICH guidelines

A validated stability indicating assay method was developed for the estimation of drotaverine HCl in the presence of its degradation products. The best separation of analyte was achieved in the C8 analytical column at ambient temperature using a mobile phase composition of methanol and ammonium acetate (75:25) in isocratic mode. The flow rate and the detection wavelength were set at 0.9 ml/min and 308 nm, respectively. The drug gives peak at RT 7.483 min and the forced degradation studies gave three degradation products peaks in which two degradation products (RT 4.202 and 5.010 min) were obtained from alkaline hydrolysis and the third product from neutral hydrolysis of the drug and was eluted at RT 5.842 min. The limit of detection (LOD) and limit of quantitation (LOQ) of the developed method was found to be 0.4 µg /ml and 1.4 µg/ml respectively. The validation results obtained from the analysis reveals that the developed method is simple, accurate, precise, specific and selective.Colegio de Farmacéuticos de la Provincia de Buenos Aire

QSAR studies of cytotoxic acridine 5,7-diones: A comparative study using P-VSA descriptors and topological descriptors

177-184A comparative QSAR study of a set of reported acridine 5,7-diones tested for cytotoxic activity against human colon adenocarcinoma cell line has been performed using topological descriptors and a novel set of P-VSA descriptors. The QSAR study showed that successful correlations can be achieved for cytotoxic activity of acridine 5,7-diones using P-VSA descriptors (R>0.9, Q²>0.7) and in fact the correlations obtained with P-VSA descriptors are of comparable significance to those obtained topological descriptors. The result of the QSAR study suggests the presence of hydrophobic moieties in the molecule and is conducive for the cytotoxic activity of the acridine 5,7-diones whereas increase in molecular surface area bearing a fractional negative charge is detrimental to the biological activity. Additionally, presence of heteroatoms and increase in branching in the molecule appears to have a positive influence in the cytotoxic activity of the acridine 5,7-diones

QSAR Studies of 6-Amino Uracil Base Analogues: A Thymidine Phosphorylase Inhibitor in Cancer Therapy

A novel series of 6-amino uracil base analogue were synthesized. QSAR study was used to relate the selective nonsubstrate inhibitory activity of 6-amino uracil base analogue with various physicochemical descriptors. Stepwise multiple regression analysis was performed to find out the correlation between various physicochemical descriptors and biological activity of the compounds by using Openstat 2 version 6.5.1 and valstat statistical software. Out of the several equations developed, the best equation having the highest significance was selected for further study. The equation is able to explain 60% of total variance and are more than 95% significant as revealed by the F value

Synthesis of some coumarinyl chalcones and their antiproliferative activity against breast cancer cell lines

A series of coumarinyl chalcones derivatives were synthesized and evaluated for their antiproliferative activities on three different breast cancer cell lines (MDA-MB231, MDA-MB468, MCF7) and one non-cancer breast epithelial cell line (184B5). The coumarinyl derivatives exhibited anticancer activity against breast cancer cell lines at a micromolar range. A structure-activity relationship (SAR) analysis was performed by studying the effect of substituents on their antiproliferative activities. One of the compound 3i bearing methoxy substitutions at the R1, R2 and R3 positions of the phenyl ring showed comparable potency to the reference drug cisplatin as well as a two-fold higher selectivity for the breast cancer cell lines than 184B5 cells