Multi-targeted dihydrazones as potent biotherapeutics

Chen Li and Sridhara, M. B. and Rakesh, K. P. and Vivek, H. K. and Manukumar, H. M. and Shantharam, C. S. and Qin, Hua-Li (2018) Multi-targeted dihydrazones as potent biotherapeutics. Bioorganic Chemistry, 81. 389 - 395. ISSN 1090-2120

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Official URL: https://doi.org/10.1016/j.bioorg.2018.08.024

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 IC50 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, OCH3) favored the H+/K+-ATPase and antioxidants activity, whereas, electron withdrawing groups (F, Cl, Br and NO2) 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.

Item Type: Article
Uncontrolled Keywords: Dihydrazones, H/K-ATPase, Anti-inflammatory activity, Antioxidants, Docking study
Subjects: B Life Science > Biotechnology
Divisions: Department of > Biotechnology
Depositing User: manjula User
Date Deposited: 04 Jul 2019 06:13
Last Modified: 04 Jul 2019 06:13
URI: http://eprints.uni-mysore.ac.in/id/eprint/4585

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