Kapendra Sahu

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.

A Validated UPLC Method Used for the Determination of Trandolapril and its Degradation Products as per ICH Guidelines

In this present research work, a new stability indicating assay method was developed for the estimation of trandolapril and its degraded products by isocratic reversed phase chromatographic technique using ultra performance liq- uid chromatography. The Study involves a comprehensive stress testing of trandolapril which was carried out according to ICH guideline Q1A (R2). The drug was subjected to acid (0.1M HCl), neutral (water) and alkaline (0.1M NaOH) hydroly- sis at 80oC, as well as the drug was kept at room temperature with H2O2 for oxidative decomposition. Photolysis was car- ried out by exposing this drug into sunlight (60,000-70,000 lux) for 2 days. Additionally, the solid drug was subjected to 50oC for 60 days in a hot air oven for thermal degradation. The results reveal that the degradation products of this drug were found in alkaline medium, acidic conditions and also in neutral hydrolysis. Separation of this drug and its degrada- tion products (from various stress conditions) was successfully achieved on a BEH (bridged ethylene hybrid) C18 column utilizing water-acetonitrile in the ratio of 20:80. The flow rate and the detection wavelength for the analysis were 0.2 mL/min and 215 nm, respectively. The method was validated and the response was found to be linear in this drug concen- tration range of 0.431-2.155 � M/mL (10-50 � g/mL). The mean values (± %RSD) of slope, intercept and correlation coef- ficient were 2674262 (±0.9), 14924 (±1.02) and 0.9999 (±0.08), respectively. The %RSD values for intra- and inter-day precision studies were <1% and <2%, respectively. The recovery of this drug ranged between 98.93-100.18% from a mix- ture of degradation products. The obtained results reveal that the developed method is specific to this drug and selective to the degradation products.

COMPARATIVE STUDY OF FORCED DEGRADATION BEHAVIOR OF PRASUGREL BY UPLC AND HPLC AND THE DEVELOPMENT OF VALIDATED STABILITY INDICATING ASSAY METHOD

A novel stability-indicating ultra-performance liquid chromatographic (UPLC) assay method was developed and validated for prasugrel and its degradation products. The UPLC separation was performed on Acquity® UPLC BEH C18 column (1.7 µm, 2.1 mm × 150 mm) using isocratic mode (acetonitrile:water, 80:20 v/v) at flow rate of 0.1 mL/min and the high performance liquid chromatography (HPLC) separation was achieved on Phenomenex® C8 column using isocratic mode (acetonitrile:10 mM ammonium acetate, 85:15 v/v) at flow rate of 0.9 mL/min. Prasugrel was found to degrade significantly in hydrolytic (acid, alkali, and neutral), and oxidative stress conditions and was stable in thermal and photolytic stress conditions. The RSD (%) values calculated for the AUC of UPLC and HPLC are 0.0039 and 0.0015, respectively. The UPLC and HPLC linearity of the proposed method were investigated in the range of 10–60 µg/mL. The r2 value of UPLC and HPLC were found to be 0.9980 and 0.9983, respectively. Method detection limit (MDL) and method quantification limit (MQL) were found to be 0.20 µg/mL and 1.00 µg/mL for UPLC and 0.50 µg/mL and 1.80 µg/mL for HPLC, respectively. The RSD (%) values for intra-day and inter-day precision were <1.0%, confirming that the method is sufficiently precise. The validation studies were carried out fulfilling ICH requirements.

Synthesis, Characterization of (E)-N'-(substituted-benzylidene)isonicotinohydrazide Derivatives as Potent Antitubercular Agents

A series of 19 isonicotinic acid hydrazide derivatives has been synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv using alamar blue susceptibility test. The synthesized compounds inhibit Mycobacterium tuberculosis H37Rv strain with minimum inhibitory concentration ranging from (0.00014-0.01174 mM). Among all synthesized compounds seven derivatives 2a, 2b, 2e, 2h, 2l, 2m and 2q were more potent than isoniazid and the compound 2q emerged as the most potent derivative, being more effective than isoniazid with an (MIC 0.00023 mM) in vitro. The results demonstrated the potential and importance of developing new isoniazid derivatives against Mycobacterium infections.

Synthesis, characterization of (Z)-N-(1-(2-(2-amino-3-(dimethylamino) methyl)phenyl)-5-phenyl-1,3,4, oxadiazol-3(2H)-yl)ethanone analogs as potent antimicrobial and hydrogen peroxide scavenging agents.

A series of (Z)-N-(1-(2-(2-amino-3-((dimethylamino) methyl) phenyl)-5-phenyl-1,3,4,oxadiazol-3(2H)- yl)ethanone derivatives was prepared and studied for its antimicrobial and antioxidant activities. Among the synthesized derivatives, compounds (7c) (Z)-N-(1-(2-(2-amino-3-((dimethylamino)methyl)phenyl)-5-phenyl-1,3,4-oxadiazol-3(2H)- yl)ethylidene)-4-chloroaniline, (7g) (Z)-N-(1-(2-(2-amino-3-((dimethylamino)methyl)phenyl)-5-phenyl-1,3,4-oxadiazol- 3(2H)-yl)ethylidene)-4-nitroaniline and (7i) (Z)-N-(1-(2-(2-amino-3-((dimethylamino)methyl)phenyl)-5-phenyl-1,3,4- oxadiazol-3(2H)-yl)ethylidene)-4-methoxyaniline were found to be the most effective antimicrobial compounds. While the compounds 7c and 7g were the most potent antioxidant compounds with significant hydrogen peroxide scavenging activity.