Molecular Modeling of the Activity Relationship, Molecular Docking, ADMET-Artificial Intelligence, Molecular Dynamic Simulations of Novel Anti-Malaria Agents
نویسندگان
1 Laboratory of Chemical Physics-Materials and Molecular Modeling (LCP3M) University of Abomey-Calavi (UAC), 03 BP 3409 Cotonou-Benin
2 Laboratory of Chemical Physics-Materials and Molecular Modeling (LCP3M) University of Abomey-Calavi (UAC), 03 BP 3409 Cotonou-Benin; National High School of Applied Biosciences and Biotechnologies (ENSBBA) National University of Sciences, Technology, Engineering and Mathematics (UNSTIM) BP 486 Abomey, Sogbo-Aliho-Benin
3 Laboratory of Chemical Physics-Materials and Molecular Modeling (LCP3M) University of Abomey-Calavi (UAC), 03 BP 3409 Cotonou-Benin
4 Laboratory of Chemical Physics-Materials and Molecular Modeling (LCP3M) University of Abomey-Calavi (UAC), 03 BP 3409 Cotonou-Benin
5 Laboratory of Chemical Physics-Materials and Molecular Modeling (LCP3M) University of Abomey-Calavi (UAC), 03 BP 3409 Cotonou-Benin
6 Laboratory of Chemical Physics-Materials and Molecular Modeling (LCP3M) University of Abomey-Calavi (UAC), 03 BP 3409 Cotonou-Benin
doi
10.22036/pcr.2025.490396.2597چکیده
The plasmodium falciparum is the deadliest specie that causes the malaria. One of the best targets in malaria disease is plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS). We proposed in this work, some hypothetical antimalarial Pyrido[1,2-a]benzimidazoles that are expected to interact with targeting with PfDHFR-TS using Quantitative Structure Activity Relationship (QSAR), molecular docking and molecular dynamic simulations (MDs). To predict the anti-malaria model, we used Klopman Perajodi Gomez technique to establish a relation between electronic structure of this real serial compounds and the median inhibition concentration. The model is used to propose a 2D pharmacophore. Based on this pharmacophore, we proposed 7 hypothetical compounds and 6 among these have a lower IC50 values than all IC50 of 41 real compounds that the most active is C25H24F3N5 (mol12). The similarity between mol12 and all compounds from Infinisee database gave 130 having at least 0.87 similarity with the most active reference compound mol12. Molecular docking of these proved only 29 can be a good candidate for malaria. The QSAR, molecular docking and MDs based on binding free energy calculation MMGBSA suggested 11 potential antimalarial compounds from Infinisee database and from QSAR.
