Identification of Dipeptidyl Peptidase IV Inhibitors: Virtual Screening, Synthesis and Biological Evaluation

2014 ◽  
Vol 84 (3) ◽  
pp. 364-377 ◽  
Author(s):  
Junhao Xing ◽  
Qing Li ◽  
Shengping Zhang ◽  
Haomiao Liu ◽  
Leilei Zhao ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Dipeptidyl Peptidase ◽  
Biological Evaluation ◽  
Dipeptidyl Peptidase Iv ◽  
Dipeptidyl Peptidase Iv Inhibitors ◽  
Synthesis And Biological Evaluation

Identification of diverse dipeptidyl peptidase IV inhibitors via structure-based virtual screening

2012 ◽  
Vol 18 (9) ◽  
pp. 4033-4042 ◽  
Author(s):  
Cui Li ◽  
Weiqiang Lu ◽  
Chunhua Lu ◽  
Wen Xiao ◽  
Xu Shen ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Dipeptidyl Peptidase Iv Inhibitors

Design, Synthesis and Biological Evaluation of Spiro Cyclohexane-1,2- Quinazoline Derivatives as Potent Dipeptidyl Peptidase IV Inhibitors

2019 ◽  
Vol 19 (3) ◽  
pp. 250-269 ◽  
Author(s):  
Yasmin M. Syam ◽  
Somaia S. Abd El-Karim ◽  
Tamer Nasr ◽  
Samia A. Elseginy ◽  
Manal M. Anwar ◽  
...  
Keyword(s):  
Heterocyclic Ring ◽  
Dipeptidyl Peptidase ◽  
Biological Evaluation ◽  
Dipeptidyl Peptidase Iv ◽  
Diabetic Patients ◽  
Design Synthesis ◽  
Reference Drug ◽  
Quinazoline Derivatives ◽  
Synthesis And Biological Evaluation

Objective: Inhibition of dipeptidyl peptidase IV (DPP-4) is currently one of the most valuable and potential chemotherapeutic regimes for the medication of Type 2 Diabetes Mellitus (T2DM). Method: Based on linagliptin, this study discusses the design, synthesis and biological evaluation of spiro cyclohexane-1,2'-quinazoline scaffold hybridized with various heterocyclic ring systems through different atomic spacers as a highly potent DPP-4 inhibitors. DPP-4 enzyme assay represented that most of the target compounds are 102-103 folds more active than the reference drug linagliptin (IC50: 0.0005-0.0089 nM vs 0.77 nM; respectively). Moreover, in vivo oral hypoglycemic activity assay revealed that most of the tested candidates were more potent than the reference drug, sitagliptin, producing rapid onset with long duration of activity that extends to 24 h. Interestingly, the derivatives 11, 16, 18a and 23 showed evidence of mild cytochrome P450 3A4 (CYP3A4) inhibition (IC50; > 210 µM) and their acute toxicity (LD50) was more than 1.9 gm/kg. Molecular simulation study of the new quinazoline derivatives explained the obtained biological results. Conclusion: Finally, we conclude that our target compounds could be highly beneficial for diabetic patients in the clinic.

scholarly journals Virtual Screening of Dipeptidyl Peptidase IV Inhibitors from Zinc Database

2012 ◽  
Vol 56 (8) ◽  
pp. 31-34
Author(s):  
Phani KumarYadla ◽  
Allam Appa Rao ◽  
A. Swaroopa Rani ◽  
M. Naresh Babu
Keyword(s):  
Virtual Screening ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Zinc Database ◽  
Dipeptidyl Peptidase Iv Inhibitors
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