Multi-targeted dihydrazones as potent biotherapeutics

Abstract Hydrazone compounds were considered as a useful moiety in drug design development. Therefore, these studies were aimed at the synthesis of new dihydrazones and were screened for their in vitro H + /K + -ATPase and anti-inflammatory activities. The results revealed that compounds 9 ( 22 ± 0.62 µg/mL) , 10 ( 26 ± 0.91 µg/mL) , 15 ( 24 ± 0.44 µg/mL) , 16 ( 28 ± 0.63 µg/mL) , 17 ( 12 ± 0.38 µg/mL) , 18 ( 14 ± 0.47 µg/mL) , 19 ( 26 ± 0.54 µg/mL) , 20 ( 16 ± 0.41 µg/mL) , 25 ( 06 ± 0.68 µg/mL) and 26 ( 08 ± 0.43 µg/mL) showed excellent H + /K + -ATPase activity and their IC 50 value were lower than the standard drug Omerazole (48 ± 0.12 µg/mL). Compounds 5 ( 28 ± 0.65 µg/mL) , 6 ( 24 ± 0.61 µg/mL) , 7 ( 28 ± 0.64 µg/mL) , 8 ( 26 ± 0.45 µg/mL) , 11 ( 30 ± 0.74 µg/mL) , 12 ( 28 ± 0.40 µg/mL) , 13 ( 32 ± 0.24 µg/mL) , 14 ( 30 ± 0.55 µg/mL) and 21 ( 08 ± 0.47 µg/mL) , 22 ( 12 ± 0.47 µg/mL) , 23 ( 10 ± 0.51 µg/mL) and 24 ( 14 ± 0.84 µg/mL) showed better anti-inflammatory activity compared to standard indomethacin (44 ± 0.15 µg/mL). The structure activity relationship (SAR) showed that, electron donating groups (OH, OCH 3 ) favored the H + /K + -ATPase and antioxidants activity, whereas, electron withdrawing groups (F, Cl, Br and NO 2 ) favored the anti-inflammatory activity. Furthermore, molecular docking study was performed to investigate the binding interactions of the most active analogs with the active site of H + /K + -ATPase enzyme. Compounds 25 (G-score = −9.063) and 26 ( G-score = −8.977) showed the highest docking G-scores for H + /K + -ATPase inhibition activity.