Abiraterone

ABSTRACTA simple, Precised, Accurate method was developed for the estimation of Abiraterone by RP-HPLC technique. Chromatographic conditions used are stationary phase  Azilent  C18 (150mm x 4.6 mm, 5m )Mobile phase 0.01%KH2PO4:Acetonitrile  in the ratio of 60:40 and flow rate was maintained at 1.0 ml/min, detection wave length was 235 nm, column temperature was set to 30oC and diluent was mobile phase Conditions were finalized as optimized method. System suitability parameters were studied by injecting the standard six times and results were well under the acceptance criteria. Linearity study was carried out between 25% to150 % levels, R2 value was found to be as 0.999. Precision was found to be 0.7 for repeatability and 0.2for intermediate precision. LOD and LOQ are 1.629µg/ml and 4.937µg/ml respectively. By using above method assay of marketed formulation was carried out 100.81% was present. Degradation studies of Abiraterone were done, in all conditions purity threshold was more than purity angle and within the acceptable range .Full length method was not performed ; if it is done this method can be used for routine analysis of AbirateroneKeywords: HPLC ,  Abiraterone , Method development , ICH Guidelines  

This project utilised abiraterone as a lead molecule for further iterative design of novel anti-prostate cancer drugs which modulate the CYP17A1 receptor. The protein data bank crystallographic deposition describing the bound co-ordinates of abiraterone and the CYP17A1 enzyme was selected. Abiraterone and the CYP17A1 were examined using structure activity relationship studies; Sybyl®-X was used to generate the apo-receptor and abiraterone extract. For in silico ligand based drug design, ViCi® Hamburg screened for molecules similar to abiraterone. A protomol for CYP17A1 was generated, usingSybyl®-X, in order to probe areas of instability, within the active site region. Both abiraterone extract and the apo-receptor were later imported into X-SCORE® to calculate the ligand binding affinity and the ligand binding energy (kcal mol-1). A total of three seeds was generated using Sybyl®-X, from which de novo molecules were generated, using LigBuilder®. Novel structures divided into various families were generated having different pharmacophores and filtered in accordance to Lipinski’s rule of five. The protomol and the keysite volumes were then compared using UCSF® Chimera.1000 molecules were generated using in silico based drug design, of which 756 were Lipinski rule compliant; 99 molecules exhibited a total score of 6 or higher, when docked into the protomol. 727 de novo molecules were generated; 465 were found to be Lipinski rule compliant and hence further used in the study for pharmacophoric evaluation. Some of the de novo molecules exhibit a pKd higher than the baseline value of 7.04, for abiraterone molecule.