Department of Chemistry, Hazara University, Mansehra 21300, Khyber Pakhtunkhwa, Pakistan.
Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.
Bioorg Chem. 2019 Oct;91:103112. doi: 10.1016/j.bioorg.2019.103112. Epub 2019 Jul 9.
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 IC value ranging between 0.8 ± 0.05 and 12.50 ± 0.5 μM as compare to standard acarbose (IC = 1.70 ± 0.10 μM). Among the synthesized analogs, compound 1j, 1r, 1k, 1e, 1b and 1f having IC 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 IC value ranging between 4.10 ± 0.02 and 38.20 ± 1.10 μM as compare to standard thiourea (IC = 21.40 ± 0.21 μM). Among the synthesized analogs, compound 2k, 2a, 2h, 2j, 2f, 2e, 2g, 2b and 2l having IC 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 H, C NMR and HR-EIMS analysis. Structure activity relationship of the synthesized analogs were recognized and confirmed through molecular docking studies.
α-淀粉酶和脲酶的过度表达会导致多种并发症，如类风湿性关节炎、尿路感染、结肠癌、代谢紊乱、心血管风险和慢性肾病。为了克服这些并发症，我们合成了新型芳基腙基席夫碱/噻唑烷酮类似物作为α-淀粉酶和脲酶抑制剂。对类似物 1a-r 进行了α-淀粉酶抑制潜力的评估。所有类似物均表现出活性，其 IC 值在 0.8±0.05 和 12.50±0.5 μM 之间，与标准阿卡波糖（IC=1.70±0.10 μM）相比。在所合成的类似物中，化合物 1j、1r、1k、1e、1b 和 1f 的 IC 值分别为 0.8±0.05、0.9±0.05、1.00±0.05、1.10±0.10、1.20±0.10 和 1.30±0.10 μM，表现出优异的抑制潜力。类似物 2a-o 对脲酶活性进行了评估。所有类似物均表现出活性，其 IC 值在 4.10±0.02 和 38.20±1.10 μM 之间，与标准硫脲（IC=21.40±0.21 μM）相比。在所合成的类似物中，化合物 2k、2a、2h、2j、2f、2e、2g、2b 和 2l 的 IC 值分别为 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 和 19.80±0.60 μM，表现出优异的抑制潜力。所有化合物均通过 H、C NMR 和 HR-EIMS 分析进行了表征。通过分子对接研究，确认并证实了所合成类似物的构效关系。
