Homology modeling, docking, and ADMET studies of benzoheterocyclic 4-aminoquinolines analogs as inhibitors of

Objectives: The ongoing fight against endemic diseases is necessary due to the growing resistance of malarial parasites to widely accessible medications. Thus, there has been an ongoing search for antimalarial medications with improved efficacy. The goal of this study was to develop derivatives of benzoheterocyclic 4-aminoquinolines with enhanced activities and better binding affinities than the original compounds. Methods: Thirty-four derivatives of benzoheterocyclic 4-aminoquinolines were docked (using a model of dihydrofolate reductase-thymidylate synthase [DRTS] protein) with Molegro software to identify the compound with the minimum docking score as a design template. The generated quantitative structure-activity model was employed to estimate the activity of the designed derivatives. The derivatives were also docked to determine the most stable derivatives. Furthermore, the designed derivatives were tested for their drug-likeness and pharmacokinetic properties using SwissADME software and pkCSM web application, respectively. Results: Compound H-014, ( Conclusion: Ten derivatives of benzoheterocyclic 4-aminoquinolines were designed with improved efficacies. Derivatives that follow Lipinski and Verber rules and are mostly non-toxic and non-sensitive to the skin can be utilized in the development of effective antimalarial medications.