ABSTRACT
Thymidine phosphorylase (TP) over expression plays role in several pathological conditions, such as rheumatoid arthritis, chronic inflammatory diseases, psoriasis, and tumor angiogenesis. The inhibitor of this enzyme plays an important role in preventing the serious threat due to over expression of TP. In this regard, a series of seventeenanalogs of 3-formylcoumarin (1-17) were synthesized, characterized by 1HNMR and EI-MS and screened for thymidine phosphorylaseinhibitory activity. All analogs showed a variable degree of thymidine phosphorylase inhibition with IC50 values ranging between 0.90⯱â¯0.01 and 53.50⯱â¯1.20⯵M when compared with the standard inhibitor 7-Deazaxanthine having IC50 value 38.68⯱â¯1.12⯵M. Among the series, fifteenanalogs such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 16 and 17 showed excellent inhibition which is many folds better than the standard 7-Deazaxanthine whiletwo analogs 13 and 14 showed good inhibition. The structure activity relationship (SAR) was mainly based upon by bring about difference of substituents on phenyl ring. Molecular docking study was carried out to understand the binding interaction of the most active analogs.
Subject(s)
Coumarins/pharmacology , Enzyme Inhibitors/pharmacology , Thymidine Phosphorylase/antagonists & inhibitors , Coumarins/chemical synthesis , Coumarins/chemistry , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Humans , Molecular Structure , Structure-Activity Relationship , Thymidine Phosphorylase/metabolismABSTRACT
We have synthesized seventeen Coumarin based derivatives (1-17), characterized by 1HNMR, 13CNMR and EI-MS and evaluated for α-glucosidase inhibitory potential. Among the series, all derivatives exhibited outstanding α-glucosidase inhibition with IC50 values ranging between 1.10⯱â¯0.01 and 36.46⯱â¯0.70⯵M when compared with the standard inhibitor acarbose having IC50 value 39.45⯱â¯0.10⯵M. The most potent derivative among the series is derivative 3 having IC50 value 1.10⯱â¯0.01⯵M, which are many folds better than the standard acarbose. The structure activity relationship (SAR) was mainly based upon by bring about difference of substituent's on phenyl part. Molecular docking studies were carried out to understand the binding interaction of the most active compounds.
Subject(s)
Coumarins/pharmacology , Glycoside Hydrolase Inhibitors/pharmacology , Molecular Docking Simulation , alpha-Glucosidases/metabolism , Coumarins/chemical synthesis , Coumarins/chemistry , Dose-Response Relationship, Drug , Glycoside Hydrolase Inhibitors/chemical synthesis , Glycoside Hydrolase Inhibitors/chemistry , Molecular Structure , Saccharomyces cerevisiae/enzymology , Structure-Activity RelationshipABSTRACT
The α-amylase acts as attractive target to treat type-2 diabetes mellitus. Therefore in discovering a small molecule as α-amylase inhibitor, we have synthesized benzofuran carbohydrazide analogs (1-25), characterized through different spectroscopic techniques such as 1HNMR and EI-MS. All screened analog shows good α-amylase inhibitory potentials with IC50 value ranging between 1.078±0.19 and 2.926±0.05µM when compared with acarbose having IC50=0.62±0.22µM. Only nine analogs among the series such as analogs 3, 5, 7, 8, 10, 12, 21, 23 and 24 exhibit good inhibitory potential with IC50 values 1.644±0.128, 1.078±0.19, 1.245±0.25, 1.843±0.19, 1.350±0.24, 1.629±0.015, 1.353±0.232, 1.359±0.119 and 1.488±0.07µM when compare with standard drug acarbose. All other analogs showed good to moderate α-amylase inhibitory potentials. The SAR study was conducted on the basis of substituent difference at the phenyl ring. The binding interaction between analogs and active site of enzyme was confirmed by docking studies.
