Comparative in-silico study on the antimalarial, anti-HIV, and diuretic properties of a series of substituted bis-2-hydroxy-1,4-naphthoquinone derivatives

Lawsone is the primary compound in the Henna plant, known for its medicinal and colouring properties. This study aimed to design and evaluate new derivatives of bis-2-hydroxy-1,4-naphthoquinone with promise anti-malarial, anti-HIV, and diuretic properties by targeting specific enzymes: Plasmepsin II, HIV protease I, and carbonic anhydrase I. Using in-silico drug design tools, derivatives of bis-2-hydroxy-1,4-naphthoquinone were designed. Molecular docking analysis was carried out to evaluate binding affinity with Plasmepsin II, HIV protease I, and carbonic anhydrase I. In addition, the pharmacokinetic properties of these compounds were assessed through drug-likeness evaluations and ADMET predictions. Among the designed derivatives, compounds SK-2, SK-5, SK-6, and SK-8 demonstrated superior binding affinities. The binding energy for Plasmepsin II ranged from − 10.5 to − 10.9 kcal/mol, for HIV protease I from − 8.1 to − 8.3 kcal/mol, and for carbonic anhydrase I from − 8.4 to − 8.7 kcal/mol, surpassing both standard and native ligands. Based on binding energies and ADMET profiles, SK-6 and SK-8 were identified as promising candidates. Compounds SK-6 and SK-8 showed the potential to inhibit Plasmepsin II, HIV protease I, and carbonic anhydrase I effectively. These findings suggest their potential as therapeutic agents for malaria, and HIV, and as diuretics, warranting further investigation and validation.