1. CARBAMATES AND CYCLIC UREAS AS INHIBITORS of a-GLUCOSIDASE:
in vitro ACTIVITY TESTING AND QSAR STUDY
Ivana Jevtić1, Jelena Popović-Đorđević2, Nađa Grozdanić Stanisavljević3, Sandra Šegan4, Mario Zlatović1,
Milovan Ivanović1, Tatjana Stanojković3
1Faculty of Chemistry, University of Belgrade, 2Faculty of Agriculture, University of Belgrade,
3Institute of Oncology and Radiology of Serbia, Belgrade,
4Institute of Chemistry, Technology and Metallurgy, University of Belgrade
Diabetes mellitus type 2 (DMT2) is an endocrine disease of global proportions which is currently affecting 1 out of 12 adults in the world, with still increasing prevalence [1]. The main classes of oral antidiabetic drugs accessible today for DMT2 vary in their chemical composition, modes of action, safety profiles and tolerability (2). Some of them like sulphonylureas act as insulin secretion stimulators, while alpha-glucosidase (a-Gls) inhibitors postpone digestion and absorption of intestinal carbohydrate. During the recent years a-Gls inhibitors have been the subject of various studies in the field of medicinal chemistry. Due to the importance of antidiabetic agents and their role in controlling diabetes-related mortality, the search for newer antidiabetic drugs continues [3].
3 (±) cis
67.59±1.90 5
67.63±0.27
4 (±) trans
68.66±3.02
2 (±) trans
63.03±2.12 11
70.41±5.21
a-glucosidase 8
71.74±2.90 12
49.85±0.10 13
75.52±8.11
Acarbose*
mM=121.01±12.18 6
76.02±5.66
1 (±)cis
104.06±0.65 10
99.48±0.16 7
83.46±14.21 9
77.61±2.27
Figure 1. IC50 values [mM] of anti a-glucosidase activity of the compounds 1–13.
*Acarbose was used as the standard drug
The inhibitory activity of cyclic urea and carbamate derivatives 1−13 toward a-glucosidase (a-Gls) in in vitro assay was examined. All 13 compounds showed higher inhibitory activity (IC50) against a-glucosidase compared to antidiabetic drug acarbose, Figure 1. QSAR analysis was attempted on activity against a-glucosidase by applaying PLS (Partial Least Square) regression analysis, aiming to better understand and explane biological behaviour of studied compounds.
The studied cyclic ureas and carbamates showed promising anti a-glucosidase activity and should be further tested as potential antidiabetic drugs.
Authors acknowledge the Ministry of Education, Science and Technological Development of the Republic of Serbia
for financial support (Grant Nos , and ).
[1]. Broichhagen J, Schonberger M, Cork SC, Frank JA, Marchetti P, Bugliani M, AMJ Shapiro, Trapp S, Rutter GA, Hodson DJ,
Trauner D. Optical control of insulin release using a photoswitchable sulfonylurea. Nat Commun 2014; 5:
[2]. Krentz AJ, Bailey CJ. Oral antidiabetic agents: current role in type 2 diabetes mellitus. Drugs 2005; 65:385–411.
[3]. Mehanna A. Antidiabetic agents: past, present and future. Future Med Chem 2013; 5:411–430.