Synthesis of benzo[d]thiazole-hydrazone analogues: molecular docking and SAR studies of potential H+/K+ ATPase inhibitors and anti-inflammatory agents

Abstract

A series of new benzo[d]thiazole-hydrazones were synthesized and characterized by analytical and spectroscopic techniques. All the compounds were screened for their in vitro inhibition of H⁺/K⁺ ATPase and anti-inflammatory effects. The results revealed that compounds 6–8, 13–15, 18–20, 22, 23 and 27–30 displayed excellent inhibitory activity against H⁺/K⁺ ATPase, and their IC₅₀ values were lower than those of the standard compound omeprazole. Compounds 2–5, 9–12, 28 and 30 exhibited better anti-inflammatory activity in comparison to the standard compound indomethacin. Studies of the structure–activity relationship (SAR) showed that electron-donating groups (OH and OCH₃) favored inhibitory activity against H⁺/K⁺ ATPase, whereas electron-withdrawing groups (F, Cl, Br and NO₂) favored anti-inflammatory activity, and derivatives with both electron-donating (OH and OCH₃) and electron-withdrawing (Br) groups (16–18) displayed reasonable activity, whereas aliphatic analogues (24–26) exhibited less activity and heterocyclic analogues (27–30) displayed moderate activity in both biological studies. Molecular docking studies were performed for all the synthesized compounds, among which compounds 19 and 20 exhibited the highest docking scores for inhibitory activity against H⁺/K⁺ ATPase, whereas compounds 10 and 12 displayed the highest docking scores for anti-inflammatory activity.