Study of Molecular Docking, Molecular Dynamic and Toxicity Prediction of Several Quinoline Alkaloid Derivatives as a Bruton Tyrosine Kinase Inhibitor as Anti-Leukemia

Abstract

Quinoline alkaloid and its derivatives play a vital role in the development of new therapeutic agents. Cinnoline structure has similarities with quinoline alkaloid compound and has the potential to inhibit Bruton’s Tyrosine Kinase (BTK) in leukemia treatment. This research aims to study the interaction of several quinoline alkaloids with BTK and to predict the toxicity to ensure their safety. This study was carried out using computational studies, including molecular docking, molecular dynamics simulation, and toxicity prediction, to assess the compound’s activity towards BTK and their toxicity. Molecular docking simulations showed that ten compounds (S1, S2, S4, S5, S8, S13, S14, S16, S17, and S20) had the best affinity to BTK. Molecular dynamics simulations to these ten compounds showed that only seven compounds (S1, S5, S8, S13, S16, S17, and S20) could stabilize the interaction towards BTK with RMSD and RMSF value of 0.5 ± 2 Å and 0.5 ± 6, 5 Å, respectively. Toxicity prediction results showed that these quinoline alkaloids had various toxicity characteristics, but most were not carcinogens and mutagens (S4, S5, S6, S7, S8, S10 S11, S12, S14, and S15). It can be concluded that Yukositrin (S8) has the most potential affinity towards BTK, which can be used as anti-leukemia with low toxicity.
 Keywords: anti-leukemia, Bruton Tyrosine Kinase, docking, MD, quinoline alkaloids