Designing Pyrrolopyrimidine Linked Triazole Derivatives as JAK Inhibitors for Anti- Cancer Activity: Molecular Docking Analysis and ADMET Prediction

Abstract

Abstract Janus kinases (JAKs) are a family of non-receptor tyrosine kinases that play a central role in the signaling pathways of many cellular processes, including inflammation, cell growth, and differentiation. JAK inhibitors have been shown to have potential as anticancer agents. In this study, a series of pyrrolopyrimidine-linked triazole derivatives were designed and synthesized. The molecular docking studies were performed using Auto Dock Vina to evaluate the binding affinity of the compounds with JAK. The ADMET properties of the compounds were predicted using the ADMET Predictor software. The molecular docking studies showed that the compounds have a good binding affinity with JAK. The ADMET properties of the compounds were predicted to be favorable. According to a study on Passonline study, the substances will react with thioredoxin inhibitor activity with the fewest negative effects. Given that the proposed compounds only violate one of the "rules of five," it can be said that these derivatives may have oral activity. All of the proposed compounds can be regarded as safer lead molecules based on the ADMET study. based on the docking Analysis revealed that the derivatives had the lowest minimum binding energy to the protein and had a strong binding affinity. The docking results indicated that the compounds D2 and D6 respectively, would be the most potent inhibitors. Hydrophobic and hydrogen bond interactions occur between the molecules. These results suggest that the pyrrolopyrimidine-linked triazole derivatives have the potential as JAK inhibitors for anticancer activity.