α-Glucosidase inhibitory activity and cytotoxic effects of some cyclic urea and carbamate derivatives

Abstract

The inhibitory activities of selected cyclic urea and carbamate derivatives (1–13) toward α-glucosidase (α-Gls) in in vitro assay were examined in this study. All examined compounds showed higher inhibitory activity (IC50) against α-Gls compared to standard antidiabetic drug acarbose. The most potent was benzyl (3,4,5-trimethoxyphenyl)carbamate (12) with IC50 = 49.85 ± 0.10 µM. In vitro cytotoxicity of the investigated compounds was tested on three human cancer cell lines HeLa, A549 and MDA-MB-453 using MTT assay. The best antitumour activity was achieved with compound 2 (trans-5-phenethyl-1-phenylhexahydro-1H-imidazo[4,5-c]pyridin-2(3H)-one) against MDA-MB-453 human breast cancer cell line (IC50 = 83.41 ± 1.60 µM). Cyclic ureas and carbamates showed promising anti-α-glucosidase activity and should be further tested as potential antidiabetic drugs. The PLS model of preliminary QSAR study indicated that, in planing the future synthesis of more potent compounds, the newly designed should have the substituents capable of polar interactions with receptor sites in various positions, while avoiding the increase of their lipophilicity.

Synthesis and Sar Strategy of Thiazolidinedione: A Novel Approach for Cancer Treatment

“…These are the oral antidiabetic drug which acts by preventing carbohydrate metabolism [64]. Now a days, various alpha GIs inhibitors such as iminosugars, carbasugars, thiosugars and non-sugar derivatives which are used for many diseases such as lysosomal storage disorders, HIV infection and cancer [65].…”

RM1 Semiempirical Model: Chemistry, Pharmaceutical Research, Molecular Biology and Materials Science

“…Other medicinal chemistry studies employed the RM1 method to optimize the geometries of the following compounds of biological interest: a potent thiazolylhydrazone-based antitrypanosomal; 84 alkaloids obtained from Hippeastrum morelianum Lem. (Amaryllidaceae); 173 C-glucosidic ellagitannins, prepared by a biomimetic synthesis of compound 5-O-desgalloylepipunicacortein A; 187 (5Z)-5-[(5-bromo-1H-indol-3-yl)methylene]-3-(4-chlorobenzyl)-thiazolidine-2,4-dione, which is effective as pan peroxisome proliferatoractivated receptor agonist and cyclooxygenase inhibitor; 189 1,7-bis(aminoalkyl)diazachrysene derivatives, that are capable of inhibiting three unrelated pathogens: the botulinum neurotoxin serotype A light chain; Plasmodium falciparum malaria and Ebola filovirus; 190 derivatives of thiazolidinones with anti-Trypanosoma cruzi activity; 192 derivatives of the E,Z-isomers of 3-arylidene substituted flavanone, chromanone and 3-aryl substituted flavone, that exhibited biological activities for the treatment of the following types of cancer: cell lines (HL-60, NALM-6, WM-115) and normal cell line (HUVEC); 70 2-pyridyl thiazoles, that are anti-Trypanosoma cruzi agents; 193 surfactants of the type bispyridinium diexadecyl cationic gemini, which are nonviral gene-deliveries; 196 phthalimides with antiproliferative and immunomodulatory activities; 202 Aedes aegypti larvicidal based on thiosemicarbazones; 209 inhibitors of chikungunya virus (CHIKV; genus Alphavirus) protease; 210 peroxisome proliferator-activated receptor gamma (PPARγ), which is capable of regulating pathways involved in the pathogenesis of obesity and atherosclerosis; 215 a series of 4-amino-7-chloroquinoline (4,7-ACQ) compounds, that exhibited higher antimalarial activities; 216 usnic acid enamines that enhance the cytotoxic effect of camptothecin, and, therefore, are inhibitors of the tyrosyl-DNA phosphodiesterase; 218 cyclic urea and carbamate derivatives that are α-glucosidase inhibitors; 166 4-aminoquinolines as quorum sensing inhibitors in Serratia marcescens and Pseudomonas aeruginosa; 222 and a set of 77 Leishmania donovani inhibitors of N-myristoyltransferase. 224 Optimized geometries calculated by RM1 were also used as strategy to obtain initial structure for the target systems, to subsequently employ DFT and/or ab initio methods.…”

Design, Synthesis, Molecular Docking, and Kinetic Study of 3-Amino-2,4-Diarylbenzo[4,5]Imidazo[1,2-a]Pyrimidines as Novel, Potent Α-Glucosidase Inhibitor

“…Over recent decade, various heterocyclic-based compounds possessing α-glucosidase inhibitory activities have been found [13][14][15][16][17][18][19][20][21][22][23][24] . For example, several pyrimidine derivatives have shown excellent inhibition potency [25][26][27][28] .…”