Posted by admin on Nov 30, 2023 in |
Breast cancer refers to cancer emerging from breast tissue, commonly from the lobules that supply the ducts with milk or from the inner linings of milk ducts. Due to the mutation of DNA or RNA from the normal cells and abnormal genes when inherited, cancer cells are evolved. LMTK3 (lemur tyrosine kinase 3) has emerged as an important player in breast cancer, contributing to the advancement of disease and the acquisition of resistance to therapy through a strikingly complex set of mechanisms. This prompted us to design newer LMTK3 inhibitors as efficient therapeutic drugs for the treatment of Breast cancer. Based on the common pharmacophoric features for the inhibition of LMTK3, a series of leads were designed using computational methods. A virtual library consisting of newly designed 100 molecules as LMTK3 inhibitors was constructed. Based on these facts, a scaffold library has been created with 100 newly designed ligands containing aromatic rings, Imidazole, pyrrole, indole, benzimidazole, morpholine, benzothiazole, pyrazine, quinoxaline, pyridine, indolinone, oxazole, quinolizine as LMTK3 inhibitors. The binding...
Read More
Posted by admin on Nov 30, 2023 in |
“Quality by Design” (QbD) serves as a bridge between industry and drug regulatory authorities to move towards a scientific, risk based holistic and proactive approach for development of pharmaceutical products. So, the present work describes the development of RP-HPLC method for simultaneous estimation of azelnidipine and telmisartan in pharmaceutical dosage form by QbD approach. The Box-Behnken design was used for screening where the effect of flow rate, % organic phase and temperature on retention time, resolution, number of theoretical plates (NTP) and symmetry factor (critical quality attributes) was evaluated. Chromatogram was run through Discovery C18 250 x 4.6 mm, 5m. Mobile phase containing 0.01N Ortho Phosphoric Acid: Acetonitrile taken in the ratio of 53.8:46.2V/V was pumped through column at a flow rate of 0.9 ml/min. The developed method was validated according to guidelines of the International Conference on Harmonization (ICH). Hence, the developed method using QbD approach was better understood that, reduces the time and cost of the...
Read More
Posted by admin on Nov 30, 2023 in |
Androgenic hormones such as testosterone and dihydrotestosterone are essential for the progression of the prostate gland. Overexpression of androgenic receptors is responsible for the proliferation of prostate tumours and androgenic receptors are an essential target in prostate cancer therapy. Flutamide was the first Nonsteroidal androgen receptor antagonist used to treat prostate cancer, but it causes side effects such as hepatotoxicity. This study aims to develop less toxic compounds using a bioisosteric approach by replacing groups such as nitro, trifluoromethyl and aryl of Flutamide drug and to improve pharmacokinetic and toxicity prediction as well as docking studies of newly generated bioisosteres. The Lipinski rule of five was followed. In the docking study, docking scores were obtained in the range of -7.76 to -9.75 Kcal/mol. All ligands docked inside the binding pocket region share a shape that is complementary to the androgen receptor. Among the selected bioisosteres and flutamide, the common amino acid residue 746Val plays a key role in the activity and binding affinity. Based on their QED score, toxicity...
Read More
Posted by admin on Nov 30, 2023 in |
Climbazole is a topical antifungal agent commonly used to treat human fungal skin infections such as dandruff and eczema. The goal of research work was to develop and validate a simple, precise, quick, and highly efficient UV spectrophotometric approach for quantifying Climbazole in bulk and shampoo dosage form. The quantification was completed using a twin beam UV spectrophotometer at 222 nm and ethanol (99.9%) as the solvent for the estimate. The Climbazole calibration curve exhibit strong correlation coefficient (R2=0.9938) and high linearity in the range of 5–25 µg/ml concentrations. The accuracy was found to be between 98.21%- 99.83%. The accuracy of the approach was proved by the percent relative standard deviation being less than 2.0%. It was observed that the intraday and interday precision found within acceptable ranges. The method’s sensitivity was assessed using the detection limit and quantification limit, which were discovered to be 2.37 µg/ml and 7.20 µg/ml, respectively. In this paper, we introduce a UV-spectrophotometric technique for investigating Climbazole using ethanol as solvent. The suggested method demonstrated excellent...
Read More
Posted by admin on Nov 30, 2023 in |
A highly sensitive, simple, accurate and precise HPLC-ESI-MS/MS method was developed and validated for the quantitative determination of talazoparib in biological matrices. The present study describes the determination of Talazoparib using validated protein precipitation method from human plasma employing Talazoparib 13C D4 as internal standard by electron spray ionization technique. Combination of 0.1% v/v formic acid and methanol (25:75) % v/v was used as mobile phase. Ascentis Express C18 (50 mm × 4.6 mm, 2.7 µm) column was employed for the separation and the run time was 3 minutes. Flow rate was set at 0.6 ml/min and column oven temperature at 40°C for the chromatographic separation method. 10µl injection volume was selected for mass spectrometer to obtain good ionisation. Parent (Q1) and Product (Q3) ion mass transitions for Talazoparib and Talazoparib-13C-D4 were found at m/z 381.5®180.5 and 386.4®180.5 respectively. The linear regression data for the calibration plot showed a good relationship with high correlation coefficient. Correlation coefficient (r2) value from the standard curve (5-10000 pg/ml) found to be more...
Read More
