Antimalarial potential of naphthalene-sulfonic acid derivatives: Molecular electronic properties, vibrational assignments, and in-silico molecular docking studies

The need to discover, design and develop novel anti-malaria agent that are capable of treating and providing prophylaxis cover for malaria infections has become paramount. Herein, four novel derivatives of naphthalene-2-sulfonic acid: 5-amino-3-((4-formylphenyl)diazenyl)-4-hydroxynaphthalene-2,7-disulfonic acid (AZDH1), 7-amino-3-((4-formylphenyl)diazenyl)-4-hydroxynaphathalene-2-sulfonic acid (AZDH2), 6-amino-3-((4-formylphenyl)diazenyl)-4-hydroxynaphthalene-2-sulfonic acid (AZDH3), 5-((4-formylphenyl)diazenyl)-6-nitronapthalene-2-sulfonic acid (AZDH4) have been synthesized and characterized using FT-IR, UV-vis, and NMR spectroscopic techniques. The studied compounds were modeled for their molecular electronic structural properties and antimalarial activity using first principle density functional theory (DFT) at the B3LYP/6-31++G(d, p) level of theory and in-silico molecular docking. The influence of solvation on the vibrational and excited states characteristics of the studied compounds were conducted with the intentions of assessing possible hydration and changes in absorptivity of –OH, -NH₂, -SO₃, and C=O functional groups in different media. The molecular docking results show that the combination of the four compounds when docked with proteins: 1RQJ, 3J7A and 6MUW revealed a mean binding affinity of −9.4, −7.6 and −8.4 kcal/mol, respectively. Because the high binding affinities indicate a high reactivity compared to the standard (artesunate), it can be said that the studied compounds are capable of inducing a protective influence against the P. berghei- exerting inflammatory response by inhibiting NF-κB nuclear translocation that results to endothelial cell activation and the subsequent expression of ICAM-1 through an autonomous mechanism that kills the plasmodium parasite.