Comparative Theoretical Study of the Pharmacophores of Several Antimalarial Drugs Approved for Sale on the Pharmaceutical Market in Côte d'Ivoire

Abstract

Malaria remains a public health problem requiring pharmacological innovation in antimalarial drugs. Therefore, their study is of great interest in providing a rapid and less costly route to the development of new, more effective antimalarial drugs. The molecular dipole moment and stability parameters were calculated using DFT/B3LYP/6-31+G (d, p) theory to assess the solubility and chemical stability of nine antimalarial pharmacophores. Lipinski's parameters and the Topological Polar Surface Area (TPSA) were also calculated to evaluate their therapeutic quality. The results obtained reveal that all these pharmacophores are of interesting therapeutic quality. The fat-soluble ones (P-4A1, P-Al2, P-Al3, P-Ar4, P-Hy9) are for prevention, while the ones that are soluble in blood plasma (P-Bi5, P-8A6, P-Fa7, P-Fo8) are for treatment. The higher TPSA value of P-Bi5 (97.78 Ǻ2) predicts that it will remain in the environment for a long time. P-Bi5 (Proguanil, Chloroproguanil) is identified as more promising for curative treatments and P-Hy9 (Atovoquone) for preventive treatments. These results are of great scientific importance in the context of combining antimalarial drugs in the fight against malaria by exploring a possible combination of Proguanil and Atovoquone to circumvent the side effects of Chloroproguanil.