Mounika Peddaguravagari, Shelby Mariya, K S Chethan, Kumar Honnavalli Yogish, Gurupadayya Bannimath
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India.
Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India.
Bioanalysis. 2025 Apr;17(7):445-453. doi: 10.1080/17576180.2025.2481023. Epub 2025 Mar 24.
The main purpose of the study is to establish Bioanalytical method development for enantiomeric divergence and Stereoselective Pharmacokinetic activity of 1-(4-bromophenyl)-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-sulfonamide(B06).
Isoquinoline derivatives have various activities like anticancer, anti-convulsant etc. The proposed project is mainly focused on anti-cancer activity of the synthesized B-06 compound as it shown very good cytotoxicity activity on MBA-MD-231 and MCF-7 cell lines by using SRB assay.
The specified project was completed with HPLC and an amylose chiral column. The bioanalytical approach was developed and tested using Wister Albino rats in compliance with USFDA Guidelines and expanded to include pharmacokinetic activities.
Data that had previously been published was used to design the B06 compound. RT of 9.578 and 7.076 minutes were observed for (R) &; (S) B06 Compound. Within-run and between-run precision for S-enantiomer varied from 0.28 to 6.078%, while R-enantiomer was found to range from 0.34 to 6.08%. Recovery rates ranged from 80.06% to 92.60% for both enantiomers. Pharmacokinetic investigations were developed and validated by using PKSolver software with Microsoft Excel.
We successfully established optimized bioanalytical method for pharmacokinetic study were both the enantiomers were properly separated. In pharmacokinetic activity we found that the enantiomers are non-stereoselective having same absorption rate.
本研究的主要目的是建立用于1-(4-溴苯基)-6,7-二甲氧基-3,4-二氢异喹啉-2(1H)-磺酰胺(B06)对映体差异和立体选择性药代动力学活性的生物分析方法。
异喹啉衍生物具有多种活性,如抗癌、抗惊厥等。拟开展的项目主要聚焦于合成的B-06化合物的抗癌活性,因为通过SRB测定法,它对MBA-MD-231和MCF-7细胞系显示出非常好的细胞毒性活性。
该特定项目通过高效液相色谱法和直链淀粉手性柱完成。按照美国食品药品监督管理局的指南,使用Wistar白化大鼠建立并测试了生物分析方法,并将其扩展至包括药代动力学活性。
先前发表的数据用于设计B06化合物。观察到(R)和(S)B06化合物的保留时间分别为9.578分钟和7.076分钟。S-对映体的批内和批间精密度在0.28%至6.078%之间,而R-对映体的精密度在0.34%至6.08%之间。两种对映体的回收率在80.06%至92.60%之间。使用带有Microsoft Excel的PKSolver软件开展并验证了药代动力学研究。
我们成功建立了用于药代动力学研究的优化生物分析方法,两种对映体得到了恰当分离。在药代动力学活性方面,我们发现对映体是非立体选择性的,具有相同的吸收率。