Novel Aromatic Sulfonimides With Antidyslipidemic Activity: Facile Synthesis, In Silico, and In Vivo Studies

Sulfonimides, with two sulfone groups on the same nitrogen atom, have emerged as novel chemical entities with potential antidyslipidemic activity. In this study, facile synthesis of nine novel aromatic sulfonimides (A1–A9) were performed, along with 1 H, 13 C NMR, and mass spectrometry characterization. Molecular docking studies of the derivatives against two possible target enzymes CETP and HMGR were performed. All derivatives possessed low binding energies toward CETP, with A9 and A1 showing the least binding energy (−11.55 and −9.65 kcal mol −1 , respectively) compared to the reference torcetrapib (−7.87 kcal mol −1 ). Similarly, all derivatives had comparable binding energies toward HMGR as for CETP. Notably, A9 showed the least value (−8.08 kcal mol −1 ) compared to the reference lovastatin (−7.70 kcal mol −1 ). The drug likeness of A9 and A1 derivatives was assessed by ADMET analysis. The antidyslipidemic activity of A9 and A1 derivatives was evaluated in vivo using acute hyperlipidemic rat model induced by Poloxamer 407, using lovastatin as control. Lovastatin, A1, and A9 significantly decreased total cholesterol levels after 24 h administration by 640.8%, 471.4%, and 672.6% respectively. Additionally, all derivatives were found non‐cytotoxic on the human normal fibroblast cells, which allows pursuing of A9 and A1 in further biological assessments.