Synthesis of new arylhydrazide bearing Schiff bases/thiazolidinone: α-Amylase, urease activities and their molecular docking studies

• Published in: Bioorganic Chemistry
• Main Author: Rahim F.; Taha M.; Ullah H.; Wadood A.; Selvaraj M.; Rab A.; Sajid M.; Shah S.A.A.; Uddin N.; Gollapalli M.
• Format: Article
• Language: English
• Published: Academic Press Inc. 2019
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85069638917&doi=10.1016%2fj.bioorg.2019.103112&partnerID=40&md5=bc3cbb4911be951df4e531ef4d290684

Alpha-amylase and urease enzyme over expression endorses various complications like rheumatoid arthritis, urinary tract infection, colon cancer, metabolic disorder, cardiovascular risk, and chronic kidney disease. To overcome these complications, we have synthesized new arylhydrazide bearing Schiff bases/thiazolidinone analogues as α-amylase and urease inhibitors. The analogues 1a-r were evaluated for α-amylase inhibitory potential. All analogues were found active and show IC50 value ranging between 0.8 ± 0.05 and 12.50 ± 0.5 μM as compare to standard acarbose (IC50 = 1.70 ± 0.10 μM). Among the synthesized analogs, compound 1j, 1r, 1k, 1e, 1b and 1f having IC50 values 0.8 ± 0.05, 0.9 ± 0.05, 1.00 ± 0.05, 1.10 ± 0.10, 1.20 ± 0.10 and 1.30 ± 0.10 μM respectively showed an excellent inhibitory potential. Analogs 2a-o were evaluated against urease activity. All analogues were found active and show IC50 value ranging between 4.10 ± 0.02 and 38.20 ± 1.10 μM as compare to standard thiourea (IC50 = 21.40 ± 0.21 μM). Among the synthesized analogs, compound 2k, 2a, 2h, 2j, 2f, 2e, 2g, 2b and 2l having IC50 values 4.10 ± 0.02, 4.60 ± 0.02, 4.70 ± 0.03, 5.40 ± 0.02, 6.70 ± 0.05, 8.30 ± 0.3, 11.20 ± 0.04, 16.90 ± 0.8 and 19.80 ± 0.60 μM respectively showed an excellent inhibitory potential. All compounds were characterized through 1H, 13C NMR and HR-EIMS analysis. Structure activity relationship of the synthesized analogs were recognized and confirmed through molecular docking studies. © 2019 Elsevier Inc.