HUBUNGAN KUANTITATIF STRUKTUR DAN AKTIVITAS SENYAWA 1,4-DISUBSTITUSI PIPERAZIN BERINTI INDOL SEBAGAI SENYAWA SITOTOKSIK

• Main Author: Endang N, Fitria
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/64449
• Institution: Institut Teknologi Bandung

Background and purpose: Tubulin is a protein that plays an important role in cell drvision. This protein is widely used as a target in cancer treatment. One of the compounds that work on this protein is indole-based 1,4-disubstituted piperazine derivatives. Mechanism of action of these compounds is by binding to receptors on B-tubulin that disrupt microtubule formation and mitotic thread, thus the cell cycle is blocked at mitotic phase. The purpose of this study is to obtain the best QSAR equation for the compound of indole-based I,4-disubstituted piperazine derivatives as well as designing new derivatives those have predicted IC50 better than the parent compounds based on QSAR equation. Methods: This study includes several stages, namely: molecular modeling, geometry optimization, calculation of predictors, statistical analysis, validation, determination of the best QSAR equations, modeling of new compounds, and docking. Results: The statistical analysis and validation showed that the best equation consists of 3 predictors. Best QSAR equation for indole-based 1,4-disubstituted piperazine derivatives against it's cytotoxic activity is 1050 = 434.57 (±143.I15) .4- 3.896 (± 0.598) AM1dipole 50.785 0,17.229) AM1 HOMO — 3.078 (1.723) logP with statistical parameter values r2 = 0.861; F = 20.684; and q2 0_8612. By using the equation, it can be predicted the activity (IC50) of the new compounds. The 12 new compounds have 1050 values better than the parent compound. This compound is then docked to determine the stability and affinity values. Conclusion: The best QSAR equation for indole-based 1,4-disubstituted piperazine derivatives against it's cytotoxic activity is IC50 = 434.57 (+143.115) 3.896 (± 0.598) AMI dipole + 50.785 (±17.229) AM) HOMO — 3.078 (,1_- 0.723) logP. There are 12 compounds that have greater activity, and the most potential is compund K.