EX VIVO ANTICOAGULANT ACTIVITY OF 1, 3, 4-OXADIAZOLE DERIVATIVES

Objective: The present medication for the management of arterial thromboembolism (ATE) disorders by anticoagulant therapy highlights its lacunae due to recurrent ATE episodes and indicates the need for better anticoagulant agents with clinical advantage.Methods: The anticoagulant study was performed for increase in prothrombin time (PT) and activated partial thromboplastin time (aPTT) at a test dose of 25 mg kg-1.Results: The results of ex vivo anticoagulant evaluation revealed that the tested compounds 3a-3q did not exhibit a significant increase in PT with respect to acenocoumarol (1 mg kg-1) employed as the reference drug for increase in PT. While the compounds, 3a-3q exhibited minimal increase in aPTT in comparison to unfractionated heparin (500 IU kg-1) employed as the reference drug for increase in aPTT. Among all the tested compounds, only compound 3q exhibited moderate anticoagulant activity with an increase in PT (33 ± 0.4 s) to that of the reference drug acenocoumarol (48 ± 0.5 s).Conclusion: The anticoagulant efficacy investigation highlights that the synthesized compound 3q could be considered for further clinical studies to ascertain its possible hit as anticoagulant agents.Â

NOVEL UV SPECTROPHOTOMETRIC METHOD FOR THE DETERMINATION OF TERIFLUNOMIDE IN TABLET DOSAGE FORM

Objective: The current work is intended towards the development of a novel, simple, and precise UV spectrophotometric method for the estimation of teriflunomide (TEF) present in the marketed formulation. Methods: Acetonitrile was used as asolvent and the absorbance of the drug was measured at the absorbance maxima of TEF, UV 284 nm. Results: Calibration curve plotted in concentration range 5-10 µg /ml exhibited excellent linear relationship with line equation y = 0.0858x-0.0223 and r2 value of 0.9996. The method was found to comply all the validation parameters as per the ICH guideline indicating the sensitivity of the method towards analyte. Conclusion: The method can be used satisfactorily for the routine analysis of TEF present in marketed formulation

RP-UFLC METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF CLOPIDOGREL, PANTOPRAZOLE AND ROSUVASTATIN IN HUMAN PLASMA: DRUG INTERACTION STUDIES

Objectives: Objective of our present study was to develop a novel ultra fast liquid chromatographic method for quantitative simultaneous estimation of Clopidogrel, Pantoprazole & Rosuvastatin in human plasma and to validate the developed method following USFDA guidelines.Methods: In the current study, the analysis was performed on phenomenex C8 (250 × 4.6 mm, 5μm) column using phosphate buffer (pH-2.5) and acetonitrile (45: 55 v/v) as mobile phase at flow rate of 1.2 mL/min. The system consisted of a pump (Shimadzu, prominence, UFLC), with 20 µl sample injector, along with a PDA detector at a wavelength of 254, 243 nm and 220 nm for Clopidogrel, Pantoprazole and Rosuvastatin respectively. Data was compiled using Shimadzu LC Solution software.Results: In this developed method Clopidogrel, Pantoprazole & Rosuvastatin, eluted at a retention time of 2.566, 5.002 and 9.301 min respectively. The proposed method is having linearity in the concentration range from 5 to 50μg/mL of Clopidogrel, Pantoprazole & Rosuvastatin. The current method was validated with respect to accuracy, linearity; precision, lowest limit of quantification (LLOQ) and recovery according to the USFDA guidelines.  A good linear relationship over the concentration range of 5-50µg/ml was shown. Validation of the method was carried out as per the USFDA draft guidelines.Conclusion: A novel specific, accurate, precise UFLC method was developed for quantitative simultaneous estimation of Clopidogrel, Pantoprazole & Rosuvastatin in human plasma and validated. The developed method is suitable and economic for routine analysis and pharmacokinetic studies of Clopidogrel, Pantoprazole & Rosuvastatin simultaneously. The method developed was found to be precise, accurate, specific, linear and sensitive. Statistical analysis shows that the method is reproducible and selective for the estimation of Clopidogrel, Pantoprazole & Rosuvastatin in dosage form of patient plasma.Â

NOVEL HPTLC-DENSITOMETRIC METHOD FOR THE ESTIMATION OF TERIFLUNOMIDE IN TABLET DOSAGE FORM

Objective: The current work is intended towards the development of a novel, simple and precise high-performance thin layer chromatographic (HPTLC) method coupled with a densitometer for the estimation of teriflunomide (TEF) present in the marketed formulation. Methods: The chromatographic development was performed on aluminum plates coated with silica gel 60 F254 using toluene: ethyl acetate: glacial acetic acid (7.5:2: 0.5 v/v/v) as the mobile phase. Densitometric scanning was achieved at the absorbance maxima, UV 284 nm. Results: Well separated band was observed with Rf value 0.46. The calibration curve plotted in the concentration range 100-700ng/band exhibited an excellent linear relationship with the r2 value of 0.9928. The method was found to comply with all the validation parameters as per the ICH guidelines. Conclusion: The method ensures minimal use of mobile phase with minimal run time compared to other reported analytical methods. This validated method can be used by quality control laboratories for the routine quantitative analysis of tablets consisting of Teriflunomide

DESIGN, SYNTHESIS, IN VITRO ANTIOXIDANT AND IN VIVO ANTI-INFLAMMATORY ACTIVITIES OF NOVEL OXADIAZOLE DERIVATIVES

Objective: In the present study, a series of novel 1,3,4-oxadiazole derivatives (3a-3q) were designed, synthesized and evaluated for antioxidant and anti-inflammatory activities.Methods: The title compounds were designed and docked onto the COX-2 enzyme (3LN1) protein using SYBYLX 2.1. 2-substituted-5-(5-nitrobenzofuran-2-yl)-1,3,4-oxadiazole derivatives (3a-3p) were synthesized from acid catalyzed dehydrative cyclization of 5-nitrobenzofuran-2-carbohydrazide (2) with various heteroaryl/aryl/aliphatic carboxylic acid derivatives. And 5-(5-nitrobenzofuran-2-yl)-1,3,4-oxadiazole-2-thiol (3q) was synthesized on reacting the hydrazide derivative 2 with carbon disulfide. The synthesized compounds were evaluated for in vitro antioxidant property by DPPH radical scavenging assay method and in vivo anti-inflammatory activity by carrageenan induced paw edema method.Results: The synthesized 1,3,4-oxadiazole derivatives (3a-3q) were characterized on the basis of LCMS, 1HNMR [13]CNMR, IR and elemental analysis. The title compounds 3a-3q exhibited significant antioxidant efficacy ranging from 34 to 86%and the results of anti-inflammatory evaluation revealed that compounds 3c, 3e and 3d exhibited substantial anti-inflammatory activity of 72, 68 and 65%, respectively, at a dose of 50 mg kg-1.Conclusion: A significant correlation was observed between the in silico study and the anti-inflammatory results. The anti-inflammatory results highlight the synthesized compounds 3c, 3e and 3d could be considered as possible hit as therapeutic agents.Â

SPECTROPHOTOMETRIC METHOD FOR THE DETERMINATION OF AMIKACIN IN PURE AND PHARMACEUTICAL DOSAGE FORM

Objective: The aim of the study was to develop an easy, sensible and rapid method for the estimation of amikacin in both pure and marketed formulation using the spectrophotometric method.Methods: Due to lack of chromophoric group in the amikacin, it was derivatized with 0.1 mmol chloranillic acid reagent. For the estimation of amikacin, Shimadzu UV-1700 model spectrophotometer with UV probe software was used. The method was based on simple charge transfer complexation of the drug with a p-chloranillic acid reagent to give a purple coloured product which was measured at 524nm against blank solution.Results: The derivatised product of amikacin was detected at a wavelength of 524 nm. Linearity was observed with the concentration range of 20-100 µg/ml with a regression coefficient of 0.9803. Results of all the parameters were within the acceptance criteria with % RSD less than 2.Conclusion: The spectroscopic method was validated as per ICH guidelines and was found to be applicable for routine quantitative analysis of amikacin in marketed formulations also. The results of linearity, precision, accuracy LOD and LOQ were within the specified limits. The method is highly sensitive, robust, reproducible and specific.Â

7-Chloro-3-phenyl­benzo[4,5]thia­zolo[2,3-c][1,2,4]triazole

In the title compound, C14H8ClN3S, the dihedral angle between the approximately planar triple-fused ring system (r.m.s. deviation = 0.065 Å) and the pendant phenyl ring is 62.25 (5)°. In the crystal, mol­ecules are linked into infinite chains along the c-axis direction by C—H⋯N hydrogen bonds. Aromatic π–π stacking inter­actions [centroid–centroid distances = 3.7499 (8) and 3.5644 (8) Å] and weak C—H⋯π inter­actions are also observed

1-(6-Fluoro-1,3-benzothia­zol-2-yl)-3-phenyl-1H-pyrazole-4-carbaldehyde

The asymmetric unit of the title compound, C17H10FN3OS, consists of two crystallographically independent mol­ecules. In one mol­ecule, the pyrazole ring makes dihedral angles of 6.51 (7) and 34.02 (9)°, respectively, with the terminal 1,3-benzothia­zole ring system and the phenyl ring, while in the other mol­ecule these values are 6.41 (8) and 23.06 (9)°. In the crystal, the molecules are linked by weak π–π [centroid–centroid distance = 3.7069 (10) Å] and C—H⋯π inter­actions