Molecular Docking, Molecular Dynamics, and In Silico Prediction of the Toxic Potential of Primaquine Thiazolidinone Derivatives

Backkground: Primaquine thiazolidinone derivatives are proposed as promising antimalarial candidates to be tested as primaquine substitutes. Method: Molecular docking and dynamics simulations were applied in the analogues-NQO2 complexes to understand their interactions, and the toxic potential of these derivatives in a set of 16 target proteins was also studied. Results: The results of our study suggest that the interactions of five thiazolidinone primaquine derivatives with NQO2 are stronger than the interaction of primaquine and NQO2. The analogue 5nprotein complex seems to be the most stable compared with the primaquine-protein complex. The analogues 5n and 5o are predicted to be in the same class of toxic potential as primaquine. Conclusion: Their interactions with the cytochrome P450 enzymes are also predicted to be weaker, indicating that a better activity/toxicity balance compared with primaquine may be reached.